Influence Of Genetic Background Research Articles

Enhanced Novel Object Recognition and Spatial Memory in Rats Selectively Bred for High Nicotine Preference

This study examined the influence of genetic background on cognitive performance in a selectively bred high nicotine-preferring (NP) rat line. Using the novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) tests, we evaluated object memory, spatial memory, and spatial navigation in nicotine-naive NP rats compared to controls. Our results demonstrate that in the NOR test, both male and female NP rats spent more time exploring the novel object (higher discrimination index) compared to sex-matched controls. In the NLR, the discrimination index differed significantly from zero chance (no preference) in both NP males and females but not in controls, indicating enhanced spatial memory in the NP line. During MWM acquisition, the NP groups and control males took a shorter path to reach the platform compared to control females. On the probe trial, the distance traveled in the target quadrant was longer for NP males and females compared to their respective controls, suggesting enhanced spatial navigation and learning in the NP rats. The interesting preference for novel objects and locations displayed by NP rats may indicate a potential novelty-seeking phenotype in this line. These results highlight the complex interplay between genetic factors, cognitive function, and nicotine preference.

Attachment-like behavioral expressions to humans in puppies are related to oxytocin and cortisol: A comparative study of Akitas and Labrador Retrievers

This study investigated the relationship between urinary hormone concentrations and attachment-related behaviors in two dog breeds, the Akitas and Labrador Retrievers, to elucidate the hormonal and behavioral mechanisms underlying domestication and interspecies attachment to humans. By measuring cortisol and oxytocin concentrations, and conducting the Strange Situation Test (SST), we aimed to investigate breed differences in endocrine secretions associated with domestication and how these differences influence dog behavior toward humans. Our results showed significant breed differences in urinary cortisol concentrations, with Akitas exhibiting higher levels than Labrador Retrievers. This suggests a breed-specific stress response related to genetic proximity to wolves. However, oxytocin concentrations did not differ significantly, which suggests a complex interplay between factors influencing the domestication process and the formation of attachment behaviors. Behavioral observations during the SST revealed breed-specific patterns, with Labrador Retrievers showing more playful and attachment-like behaviors and Akitas showing more exploratory and passive behaviors. The study found correlations between hormones and behaviors within breeds, particularly in Labrador Retrievers, where oxytocin concentrations were associated with attachment-like behaviors, and cortisol concentrations reflected individual differences in physical activity rather than stress responses to social situations. These findings contribute to the understanding of the evolutionary and adaptive processes underlying the ability of domestic dogs to form close relationships with humans while highlighting the role of hormonal mechanisms in mediating attachment behaviors and the influence of breed-specific genetic backgrounds on these processes.

The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background.

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy.

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the PrkdcR2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of ADR nephropathy in the FVB/N strain has yet to be conducted. Our research aimed to create a novel mouse model, the FVB-PrkdcR2140C, by introducing PrkdcR2140C into the FVB/NJcl (FVB) strain. Our study showed that FVB-PrkdcR2140C mice developed severe renal damage when exposed to ADR, as evidenced by significant albuminuria and tubular injury, exceeding the levels observed in C57BL/6J (B6)-PrkdcR2140C. This indicates that the FVB/N genetic background, in combination with the R2140C mutation, strongly predisposes mice to ADR nephropathy, highlighting the influence of genetic background on disease susceptibility. Using RNA sequencing and subsequent analysis, we identified several genes whose expression is altered in response to ADR nephropathy. In particular, Mmp7, Mmp10, and Mmp12 were highlighted for their differential expression between strains and their potential role in influencing the severity of kidney damage. Further genetic analysis should lead to identifying ADR nephropathy modifier gene(s), aiding in early diagnosis and providing novel approaches to kidney disease treatment and prevention.

Host Genetic Background Influences BCG-Induced Antibodies Cross-Reactive to SARS-CoV-2 Spike Protein.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) protects against childhood tuberculosis; and unlike most vaccines, BCG broadly impacts immunity to other pathogens and even some cancers. Early in the COVID-19 pandemic, epidemiological studies identified a protective association between BCG vaccination and outcomes of SARS-CoV-2, but the associations in later studies were inconsistent. We sought possible reasons and noticed the study populations often lived in the same country. Since individuals from the same regions can share common ancestors, we hypothesized that genetic background could influence associations between BCG and SARS-CoV-2. To explore this hypothesis in a controlled environment, we performed a pilot study using Diversity Outbred mice. First, we identified amino acid sequences shared by BCG and SARS-CoV-2 spike protein. Next, we tested for IgG reactive to spike protein from BCG-vaccinated mice. Sera from some, but not all, BCG-vaccinated Diversity Outbred mice contained higher levels of IgG cross-reactive to SARS-CoV-2 spike protein than sera from BCG-vaccinated C57BL/6J inbred mice and unvaccinated mice. Although larger experimental studies are needed to obtain mechanistic insight, these findings suggest that genetic background may be an important variable contributing to different associations observed in human randomized clinical trials evaluating BCG vaccination on SARS-CoV-2 and COVID-19.

SARS-CoV-2 immune response and reinfection in vaccinated Maya and mestizo in Southeast of Mexico.

Immune response to pathogens, including coronaviruses, is influenced by HLA haplotypes. 1,2. Maya ethnic group is predominant in Yucatan peninsula, this Amerindian group present allele frequency HLA-G*01:01:02, HLA-G*01:01:01, HLA-G*01:04:01, HLA-A*68 not found in another Amerindians.3-5 Immune response to SARS-CoV-2 vaccination and reinfection particularly after Omicron variant appeared was explored in 118 vaccinated subjects with complete two shots immunization in Maya ascendant and mestizo no-Maya. 1172 epidemiological survey applied to university staff in Campeche, Mexico to evaluate reinfection, co-morbidities, variant virus, disease severity, aftermaths, clinical outcomes, age, sex, ethnicity, and vaccination shots. Multiple logistic regression, correspondence analysis, and association tests were used to analysis data. Sixteen percent of vaccinated subjects became seronegative after 11 months. We found that vaccinated Maya subjects respond with higher IgG immune response compared to no-Maya subjects, similarly women respond with higher IgG response than men (p<0.05). During an eleven-month period and after two vaccination shots, 7% of the vaccinated subjects reported a confirmed positive infection, and after the third vaccine shot a higher IgG immune response than two vaccination shots or natural infection was detected. However, we observed 23.7% reinfection in people after the third shot. This data represents almost three times the reinfection rate reported when compared to previous third vaccine shots. The increase of reinfection in vaccinated subjects was associated with circulation of Omicron variant by 71.5%. Others have reported reinfection of 40% and vaccine effectiveness of 60% during Omicron dominance.6 To understand COVID-19 severity after reinfection in vaccinated subjects and the associated variables, we carried out a multiple logistic regression, and found a strong association between less severe symptoms with Alfa and Omicron variants (B 5.3; Error 0.39; Wald 0.00; Significance 0.00; OR201). However, subjects with severe symptoms and or hospitalization correspondent to individuals with multiplex comorbidities and Gamma SARS-CoV-2 variants (B 5.06; Error 0.97; Wald 26.8; Significance 0.00; OR 158). A follow-up survey of COVID-19 recovered patients experienced diverse digestive, respiratory, cardiac, neurological, or joints involvement sequelae. We looked for SARS-CoV-2 variant and COVID-19 sequelae in a correspondence analysis. Our data suggest that Beta and Delta variants are associated with respiratory and digestive symptoms, whereas Omicron was more closely associated with joints and digestive symptoms, and finally the Gamma variant displayed wider and more diverse symptoms. Our results suggest that genetic background and gender influence IgG response to SARS-CoV-2 vaccine, and Maya ascendant has higher immune IgG response to vaccine than mestizos. Reinfection in our population studied fluctuate from 7% to 23.7% nevertheless is higher if Omicron variant is involved, but symptoms are less severe and more closely associated with joints and digestive symptoms.

Genetic background and thermal regime influence adaptation to novel environment in the seed beetle, Callosobruchus maculatus.

Climate change is associated with the increase in both the mean and variability of thermal conditions. Therefore, the use of more realistic fluctuating thermal regimes is the most appropriate laboratory method for predicting population responses to thermal heterogeneity. However, the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined differences in key life-history traits among populations of seed beetles (Callosobruchus maculatus) that evolved under either constant control conditions or in an environment with fluctuating daily temperatures. Specifically, individuals from two distinct genetic backgrounds were kept for 19 generations at one of two temperatures, a constant temperature (T = 29 °C) or a fluctuating daily cycle (Tmean = 33 °C, Tmax = 40 °C, and Tmin = 26 °C), and were assayed either in their evolved environment or in the other environment. We found that beetles that evolved in fluctuating environments but were then switched to constant 29 °C conditions had far greater lifetime reproductive success compared with beetles that were kept in their evolved environments. This increase in reproductive success suggests that beetles raised in fluctuating environments may have evolved greater thermal breadth than control condition beetles. In addition, the degree of sexual dimorphism in body size and development varied as a function of genetic background, evolved thermal environment, and current temperature conditions. These results not only highlight the value of incorporating diel fluctuations into climate research but also suggest that populations that experience variability in temperature may be better able to respond to both short- and long-term changes in environmental conditions.

Genetic background influences arterial vasomotor function in male and female mice.

The purpose of this study was to assess the influence of genetic background and sex on nitric oxide (NO)-mediated vasomotor function in arteries from different vascular territories. Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from the following mouse strains: SJL/J, DBA/2J, NZW/LacJ, and C57BL/6J. Contractile responses were assessed using the α1-adrenergic receptor agonist phenylephrine (PE, 10-9 -10-5 M). Vasorelaxation responses were assessed by examining relaxation to an endothelium-dependent vasodilator acetylcholine (ACh, 10-9 -10-5 M) and an endothelium-independent vasodilator sodium nitroprusside (SNP, 10-9 -10-5 M). To evaluate the role of NO, relaxation responses to ACh and SNP were assessed in the absence or presence of a nitric oxide synthase inhibitor (N omega-nitro-l-arginine methyl ester hydrochloride: 10-4 M). Vasomotor responses to ACh and PE varied across strains and among the arteries tested with some strains exhibiting artery-specific impairment. Results indicated some concentration-response heterogeneity in response to ACh and SNP between vessels from females and males, but no significant differences in responses to PE. Collectively, these findings indicate that vasomotor responses vary by genetic background, sex, and artery type.

Exploring the interplay between metabolomics and genetics in Parkinson's disease: Insights from ongoing research and future avenues

Parkinson's disease (PD) is a widespread neurodegenerative disorder, whose complex aetiology remains under construction. While rare variants have been associated with the monogenic PD form, most PD cases are influenced by multiple genetic and environmental aspects. Nonetheless, the pathophysiological pathways and molecular networks involved in monogenic/idiopathic PD overlap, and genetic variants are decisive in elucidating the convergent underlying mechanisms of PD. In this scenario, metabolomics has furnished a dynamic and systematic picture of the synergy between the genetic background and environmental influences that impact PD, making it a valuable tool for investigating PD-related metabolic dysfunctions. In this review, we performed a brief overview of metabolomics current research in PD, focusing on significant metabolic alterations observed in idiopathic PD from different biofluids and strata and exploring how they relate to genetic factors associated with monogenic PD. Dysregulated amino acid metabolism, lipid metabolism, and oxidative stress are the critical metabolic pathways implicated in both genetic and idiopathic PD. By merging metabolomics and genetics data, it is possible to distinguish metabolic signatures of specific genetic backgrounds and to pinpoint subgroups of PD patients who could derive personalized therapeutic benefits. This approach holds great promise for advancing PD research and developing innovative, cost-effective treatments.

Genetic background modulates phenotypic expressivity in OPA1 mutated mice, relevance to DOA pathogenesis.

Dominant optic atrophy (DOA) is mainly caused by OPA1 mutations and is characterized by the degeneration of retinal ganglion cells (RGCs), whose axons form the optic nerve. The penetrance of DOA is incomplete and the disease is marked by highly variable expressivity, ranging from asymptomatic patients to some who are totally blind or who suffer from multisystemic effects. No clear genotype-phenotype correlation has been established to date. Taken together, these observations point toward the existence of modifying genetic and/or environmental factors that modulate disease severity. Here, we investigated the influence of genetic background on DOA expressivity by switching the previously described DOA mouse model bearing the c.1065 + 5G → A Opa1 mutation from mixed C3H; C57BL/6 J to a pure C57BL/6 J background. We no longer observed retinal and optic nerve abnormalities; the findings indicated no degeneration, but rather a sex-dependent negative effect on RGC connectivity. This highlights the fact that RGC synaptic alteration might precede neuronal death, as has been proposed in other neurodegenerative diseases, providing new clinical considerations for early diagnosis as well as a new therapeutic window for DOA. Furthermore, our results demonstrate the importance of secondary genetic factors in the variability of DOA expressivity and offer a model for screening for aggravating environmental and genetic factors.

Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation.

Up to 50% of systemic lupus erythematosus (SLE) patients world-wide develop lupus nephritis (LN). In low to middle income countries and in particular in sub-Saharan Africa, where SLE is prevalent with a more aggressive course, LN and end stage renal disease is a major cause of mortality. While developed countries have the funding to invest in SLE and LN research, patients of African descent are often underrepresented in clinical trials. Thus, the complex influence of ethnicity and genetic background on outcome of LN and SLE as a whole, is not fully understood. Several pathophysiological mechanisms including major role players driving LN have been identified. A large body of literature suggest that prevention of fibrosis-which contributes to chronicity of LN-may significantly improve long-term prognosis. Bone morphogenetic protein-7 (BMP-7) was first identified as a therapeutic option in this context decades ago and evidence of its benefit in various conditions, including LN, is ever-increasing. Despite these facts, BMP-7 is not being implemented as therapy in the context of renal disease. With this review, we briefly summarise current understanding of LN pathology and discuss the evidence in support of therapeutic potential of BMP-7 in this context. Lastly, we address the obstacles that need to be overcome, before BMP-7 may become available as LN treatment.

Comparative Analysis of Structural Composition and Function of Intestinal Microbiota between Chinese Indigenous Laiwu Pigs and Commercial DLY Pigs.

Intestinal microbiota has an important impact on pig phenotypes. Previous studies mainly focused on the microbiota of feces and worldwide farmed commercial pigs, while research on the microbiota of various intestinal sections and indigenous pig breeds is very limited. This study aimed to characterize and compare the biogeography of intestinal microbiota in pigs of one Chinese indigenous breed and one commercial crossbred. In this study, we sequenced the microbiota of six intestinal segments in the grown-up pigs of a Chinese indigenous breed, Laiwu pigs, and the worldwide farmed crossbred Duroc × Landrace × Yorkshire (DLY) pigs by 16S rRNA sequencing, characterized the biogeography of intestinal microbiota, and compared the compositional and functional differences between the two breeds. The results showed that there were obvious differences in microbial structure and abundance between the small and large intestines. Laiwu pigs had higher large intestinal diversity than DLY pigs, while DLY pigs had higher small intestinal diversity than Laiwu pigs. Moreover, some specific bacterial taxa and Kyoto Encyclopedia of Genes and Genomes pathways were found to be related to the high fat deposition and good meat quality of Laiwu pigs and the high growth speed and lean meat rate of DLY pigs. This study provides an insight into the shifts in taxonomic composition, microbial diversity, and functional profile of intestinal microbiota in six intestinal segments of Laiwu and DLY pigs, which would be essential for exploring the potential influence of the host's genetic background on variation in microbiota composition and diversity.

Estimation of some immunological markers for patients with Hepatitis C and B viruses with β -thalassemia major in Babylon province

Hepatitis C, B is a severe public health problem worldwide. Thalassemia patients depend on blood transfusions throughout and are at high risk of viral infections. This study aimed to estimate the prevalence of hepatitis C infection and different clinical parameters of (HLA) in the multiplex thalassemia population. In this study, 66 patients with infectious complications beta-thalassemia were enrolled, and samples collected from the Genetic Hematology Center at Babel Women and Children Hospital in Babylon Governorate / Iraq infected with HCV, serum ferritin, PCV and splenectomy were analyzed. The overall prevalence of hepatitis B virus and HCV was 3% and 55%, respectively; 100% of patients over 10-20 years of age had hepatitis C infection, and some episodes were presented by different HLA molecules, by molecule HLA from HLA class II (HLA-DR) and HLA class I (HLAG), In this study, we review the role of the molecule and several parameters along the HLA-G and HLA-DR gene in viral hepatitis, studies of hepatitis suggest that even Human leukocyte antigen contributes to the pathogenesis of the disease. HLA classification combined with the study of the regulatory elements of genes may help understand the influence of genetic background on susceptibility to disease. Keywords: Detection of some immunological markers (HLA) for hepatitis patients and those with a previous infection with thalassemia

Genetic structure of Aedes albopictus (Diptera: Culicidae) populations in China and relationship with the knockdown resistance mutations

BackgroundMosquito control is needed to prevent dengue fever, which is mainly spread by Aedes albopictus in China. Application of insecticides is one of the main mosquito control methods; however, this approach can fail due to the knockdown resistance (kdr) gene mutation that causes decreased sensitivity to insecticides in Ae. albopictus. The kdr mutation patterns among different regions in China differ significantly. However, the underlying mechanism and factors that influence kdr mutation remain unclear. To explore the potential influence of genetic background on the development of insecticide resistance in Ae. albopictus, we analyzed the genetic structure of Ae. albopictus populations in China and its correlation with major kdr mutations.MethodsWe collected Ae. albopictus from 17 sites in 11 provinces (municipalities) across China from 2016 to 2021 and extracted the genomic DNA from individual adult mosquitoes. We selected eight microsatellite loci for genotyping, and based on microsatellite scores, we estimated intraspecific genetic diversity, population structure, and effective population size. The association between the intrapopulation genetic variation and F1534 mutation rate was evaluated by the Pearson correlation coefficient.ResultsBased on variation analysis of the microsatellite loci of 453 mosquitoes representing 17 populations throughout China, more than 90% of the variation occurred within individuals, whereas only about 9% of the variation occurred among populations, indicating that field populations of Ae. albopictus are highly polymorphic. The northern populations tended to belong to gene pool I (BJFT 60.4%, SXXA 58.4%, SDJN 56.1%, SXYC 46.8%), the eastern populations tended to belong to pool III (SH 49.5%, JZHZ 48.1%), and the southern populations tended to belong to three different gene pools. Moreover, we observed that the greater the fixation index (FST), the lower the wild-type frequency of F1534 of VSGC.ConclusionsThe degree of genetic differentiation among Ae. albopictus populations in China was low. These populations were divided into three gene pools, in which the northern and eastern pools are relatively homogeneous, while the southern gene pool is heterogeneous. The possible correlation between its genetic variations and kdr mutations is also noteworthy.Graphical

Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar-Kyoto rats.

Chronic pain is often associated with comorbid anxiety and cognitive dysfunction, negatively affecting therapeutic outcomes. The influence of genetic background on such interactions is poorly understood. The stress-hyperresponsive Wistar-Kyoto (WKY) rat strain, which models aspects of anxiety and depression, displays enhanced sensitivity to noxious stimuli and impaired cognitive function, compared with Sprague-Dawley (SD) counterparts. However, pain- and anxiety-related behaviors and cognitive impairment following induction of a persistent inflammatory state have not been investigated simultaneously in the WKY rats. Here we compared the effects of complete Freund's adjuvant (CFA)-induced persistent inflammation on pain-, negative affect- and cognition-related behaviors in WKY vs. SD rats. Male WKY and SD rats received intra-plantar injection of CFA or needle insertion (control) and, over the subsequent 4 weeks, underwent behavioral tests to assess mechanical and heat hypersensitivity, the aversive component of pain, and anxiety- and cognition-related behaviors. The CFA-injected WKY rats exhibited greater mechanical but similar heat hypersensitivity compared to SD counterparts. Neither strain displayed CFA-induced pain avoidance or anxiety-related behavior. No CFA-induced impairment was observed in social interaction or spatial memory in WKY or SD rats in the three-chamber sociability and T-maze tests, respectively, although strain differences were apparent. Reduced novel object exploration time was observed in CFA-injected SD, but not WKY, rats. However, CFA injection did not affect object recognition memory in either strain. These data indicate exacerbated baseline and CFA-induced mechanical hypersensitivity, and impairments in novel object exploration, and social and spatial memory in WKY vs. SD rats.

Association of osteoporosis risk and polymorphisms of osteoprotegerin gene T950C in postmenopausal Chinese women: A PRISMA-compliant meta-analysis.

This study aimed to assess the association between the T950C polymorphism and osteoporosis in postmenopausal Chinese women to further reduce the influence of different genetic backgrounds by meta-analysis and subgroup analysis. Through November 2022, a systematic online investigation was performed with the aid of the Cochrane Library, EMBASE, PubMed, Web of Science and the Chinese National Knowledge Infrastructure to find case-control studies looking into the correlation between the osteoprotegerin gene (OPG) T950C polymorphism and postmenopausal osteoporosis susceptibility. This study included 6 studies with a total of 1669 postmenopausal osteoporosis cases and 2992 controls. In the recessive model, postmenopausal women with the CC genotype (mutant homozygote at the T950C locus) had a lower risk of osteoporosis, indicating that the CC genotype of OPG T950C might show a preventive effect on osteoporosis after menopause. In a stratified analysis by geographic area, the population from South China had a significantly higher risk under the dominant model [CC + TC (heterozygote at the T950C locus) vs TT (wild-type homozygotes at the T950C locus): odds ratio = 1.34, 95% confidence interval = 1.17-1.54, P < .01], while the population from South China had a significantly lower risk under the recessive model (CC vs TC + TT: odds ratio = 0.79, 95% confidence interval = 0.69-0.95, P = .02). Together, the OPG T950C polymorphism may be associated with osteoporosis risk in postmenopausal Chinese women, according to this meta-analysis. Because of the study's limitations, more large-scale research is needed to corroborate these findings.

C57BL/6J and C57BL/6N mice exhibit different neuro-behaviors and sensitivity to midazolam- and propofol-induced anesthesia

Phenotypes of inbred mice are strain-dependent, indicating the important influence of genetic background in biomedical research. C57BL/6 is one of the most commonly used inbred mouse strains, and its two closely related substrains, C57BL/6J and C57BL/6N, have been separated for only about 70 years. These two substrains have accumulated genetic variations and exhibit different phenotypes, but it remains unclear whether they respond to anesthetics differently. In this study, commercially acquired wildtype C57BL/6J or C57BL/6N mice from two different sources were analyzed and compared for their response to a spectrum of anesthetics (midazolam, propofol, esketamine or isoflurane anesthesia) and their performance in a series of behavioral tests associated with neurological functions including open field test (OFT), elevated plus maze (EPM), Y maze, prepulse inhibition (PPI), tail strain test (TST) and forced swimming test (FST). Loss of the righting reflex (LORR) is used to measure the anesthetic effects. Our results suggested that the anesthesia induction time induced by either of the four anesthetics were comparable for the C57BL/6J and C57BL/6N mice. However, C57BL/6J or C57BL/6N mice do exhibit different sensitivity to midazolam and propofol. The anesthesia duration of midazolam of C57BL/6J mice was about 60% shorter than that of the C57BL/6N mice, while the LORR duration induced by propofol in C57BL/6J mice was 51% longer than that of the C57BL/6N. In comparison, the two substrains were anesthetized by esketamine or isoflurane similarly. In the behavioral analysis, the C57BL/6J mice exhibited a lower level of anxiety- and depression-like behaviors in OFT, EPM, FST and TST than the C57BL/6N mice. Locomotor activity and sensorimotor gating of these two substrains remained comparable. Our results stress the point that when selecting inbred mice for allele mutation or behavioral testing, the influence of even subtle differences in genetic background should be fully considered.

Genetic Background Influence on Hippocampal Synaptic Plasticity: Frequency-Dependent Variations between an Inbred and an Outbred Mice Strain

For almost half a century, acute hippocampal slice preparations have been widely used to investigate anti-amnesic (or promnesic) properties of drug candidates on long-term potentiation (LTP)-a cellular substrate that supports some forms of learning and memory. The large variety of transgenic mice models now available makes the choice of the genetic background when designing experiments crucially important. Furthermore, different behavioral phenotypes were reported between inbred and outbred strains. Notably, some differences in memory performance were emphasized. Despite this, investigations, unfortunately, did not explore electrophysiological properties. In this study, two stimulation paradigms were used to compare LTP in the hippocampal CA1 area of both inbred (C57BL/6) and outbred (NMRI) mice. High-frequency stimulation (HFS) revealed no strain difference, whereas theta-burst stimulation (TBS) resulted in significantly reduced LTP magnitude in NMRI mice. Additionally, we demonstrated that this reduced LTP magnitude (exhibited by NMRI mice) was due to lower responsiveness to theta-frequency during conditioning stimuli. In this paper, we discuss the anatomo-functional correlates that may explain such hippocampal synaptic plasticity divergence, although straightforward evidence is still lacking. Overall, our results support the prime importance of considering the animal model related to the intended electrophysiological experiments and the scientific issues to be addressed.

Influential factors and transcriptome analyses of immature diploid embryo anthocyanin accumulation in maize

BackgroundAnthocyanins are widely applied as a marker for haploid identification after haploid induction in maize. However, the factors affecting anthocyanin biosynthesis in immature embryos and the genes regulating this process remain unclear.ResultsIn this study, we analyzed the influence of genetic background of the male and female parents, embryo age and light exposure on anthocyanin accumulation in embryos. The results showed that light exposure was the most crucial factor enhancing the pigmentation of immature embryos. The identification accuracy of haploid embryos reached 96.4% after light exposure, but was only 11.0% following dark treatment. The total anthocyanin content was 7-fold higher in immature embryos cultured for 24 h under light conditions compared to embryos cultured in the dark. Transcriptome analysis revealed that the differentially expressed genes between immature embryos cultured for 24 h in dark and light chambers were significantly enriched in the pathways of flavonoid, flavone, flavonol and anthocyanin biosynthesis. Among the genes involved in anthocyanin biosynthesis, five up-regulated genes were identified: F3H, DFR, ANS, F3′H and the MYB transcription factor-encoding gene C1. The expression patterns of 14 selected genes were confirmed using quantitative reverse transcription-polymerase chain reaction.ConclusionLight is the most important factor facilitating anthocyanin accumulation in immature embryos. After 24 h of exposure to light, the expression levels of the structural genes F3H, DFR, ANS, F3′H and transcription factor gene C1 were significantly up-regulated. This study provides new insight into the factors and key genes regulating anthocyanin biosynthesis in immature embryos, and supports improved efficiency of immature haploid embryo selection during doubled haploid breeding of maize.

Echocardiography phenotyping in murine genetic reference population of BXD strains reveals significant QTLs associated with cardiac function and morphology.

The genetic reference population of recombinant inbred BXD mice has been derived from crosses between C57BL/6J and DBA/2J strains. The DBA/2J parent exhibits cardiomyopathy phenotypes, whereas C57BL/6J has normal heart. BXD mice are sequenced for studying genetic interactions in cardiomyopathies. The study aimed to assess cardiomyopathy traits in BXDs and investigate the quantitative genetic architecture of those traits. Echocardiography, blood pressure, and cardiomyocyte size parameters obtained from 44 strains of BXD family (n > 5/sex) at 4-5 mo of age were associated with heart transcriptomes and expression quantitative trait loci (eQTL) mapping was performed. More than twofold variance in ejection fraction (EF%), fractional shortening (FS%), left ventricular volumes (LVVols), internal dimensions (LVIDs), mass (LVM), and posterior wall (LVPW) thickness was found among BXDs. In male BXDs, eQTL mapping identified Ndrg4 on chromosome 8 QTL to be positively correlated with LVVol and LVID and negatively associated with cardiomyocyte diameter. In female BXDs, significant QTLs were found on chromosomes 7 and 3 to be associated with LVPW and EF% and FS%, respectively, and Josd2, Dap3, and Tpm3 were predicted as strong candidate genes. Our study found variable cardiovascular traits among BXD strains and identified multiple associated QTLs, suggesting an influence of genetic background on expression of echocardiographic and cardiomyocyte diameter traits. Increased LVVol and reduced EF% and FS% represented dilated cardiomyopathy, whereas increased LV mass and wall thickness indicated hypertrophic cardiomyopathy traits. The BXD family is ideal for identifying candidate genes, causal and modifier, that influence cardiovascular phenotypes.NEW & NOTEWORTHY This study aimed to establish a cardiac phenotype-genotype correlation in murine genetic reference population of BXD RI strains by phenotyping the echocardiography, blood pressure, and cardiomyocyte diameter traits and associating each collected phenotype with genetic background. Our study identified several QTLs and candidate genes that have significant association with cardiac hypertrophy, ventricular dilation, and function including systolic hyperfunction and dysfunction.