Dwarf Hamster Research Articles

The Roborovski Dwarf Hamster – A Highly Susceptible Model for a Rapid and Fatal Course of SARS-CoV-2 Infection

The COVID-19 pandemic caused by SARS-CoV-2 has precipitated an unprecedented and yet unresolved crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, no species examined so far develops robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, we compare the susceptibility of three dwarf hamster species (Phodopus spp.) to SARS-CoV-2 and introduce the Roborovski dwarf hamster (P. roborovskii) as a highly susceptible COVID-19 model with consistent and fulminant clinical signs. Particularly, this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection, but so far not reproduced in any experimentally infected animal. We therefore propose the Roborovski dwarf hamster as an ideal model to examine the efficacy and safety of live attenuated vaccine candidates and novel therapeutics, particularly for their use in highly susceptible individuals.

Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis.

Photoperiod regulates the seasonal reproductive rhythms of mammals by influencing the development and function of sexual organs; however, the underlying mechanism remains unclear. We examined the morphology and functioning of the main sex organs of striped dwarf hamsters (Cricetulus barabensis) under different photoperiods (short daylight [SD], moderate daylight [MD], and long daylight [LD]) and further investigated the underlying molecular mechanisms. There was an inverse correlation between blood melatonin levels and photoperiod in the order SD > MD > LD. Decreases in body and tissue weights were observed under SD, whereas testis and epididymis weights between MD and LD were comparable. The diameters of the spermatogenic tubules, thickness of the spermatogenic epithelium, and the number of spermatogonia and Sertoli cells decreased under SD, whereas the serum-luteinizing hormone, follicle-stimulating hormone, and fecal testosterone concentrations decreased under LD. In SD, bax/bcl2 protein expression increased in the testes and decreased in the epididymides, whereas LC3II/LC3I remained unchanged in the testes and increased in the epididymides compared with the MD group. In LD, bax/bcl2 and LC3II/LC3I protein expression levels were unchanged in the testes but were decreased in the epididymides. In SD and LD, adenosine triphosphate synthase and citrate synthase protein expression levels were unchanged in the testes but were decreased in the epididymides. Drp1 and Mff protein expression increased in the testes and decreased in the epididymides. Overall, different regulatory mechanisms in the testis and epididymis led to degeneration under SD and maintenance under LD, preferentially protecting mitochondrial function in the testis by regulating mitochondrial fission.

Molecular characterization of Calodium hepaticum in grey dwarf hamster (Cricetulus migratorius).

Calodium hepaticum (Bancroft, 1893) Moravec, 1982 (Syn. Capillaria hepatica) is a zoonotic nematode that causes hepatic capillariosis, an uncommon zoonotic infection. The nematode is globally distributed and parasitizes the liver of mammals, mainly Muroidea. Cricetulus migratorius Pallas, 1773 (Cricetinae) was rarely reported as a host for C. hepaticum. In Turkey, C. hepaticum was recorded in three rodent species; Rattus rattus, R. norvegicus, and Apodemus flavicollis. In this study, C. migratorius (grey dwarf hamster) has been identified as a new host species for C. hepaticum in Turkey. The parasite was identified by morphological, histological, and molecular methods and the phylogenetic relationships of C. hepaticum collected from different hosts were revealed. This is the first molecular characterization of C. hepaticum from a grey dwarf hamster.

Photoperiod Affects Harderian Gland Morphology and Secretion in Female Cricetulus barabensis: Autophagy, Apoptosis, and Mitochondria.

Photoperiod is an important factor of mammalian seasonal rhythm. The Harderian gland (HG) appears to act as a “standby” structure of the retinal-pineal axis, mediating light signals in vitro and neuroendocrine regulation in vivo; however, the effect of photoperiod on the HG is not clear. Here, we studied morphological differences in the HG of female striped dwarf hamsters (Cricetulus barabensis), a small mammal that experiences an annual rhythm, under different photoperiods (i.e., SP, short photoperiod; MP, moderate photoperiod; LP, long photoperiod), and further investigated the molecular mechanisms related to these morphological differences. Results showed that body weight, carcass weight, and HG weight were higher in the SP and LP groups than that in the MP group. Protein expression of hydroxyindole-o-methyltransferase, a key enzyme in melatonin synthesis, was higher in the SP group than in the other two groups. Somatostatin showed highest expression in the LP group. Furthermore, comparison of changes in the HG ultrastructure demonstrated autolysosome formation in the SP group. Protein aggregation and mRNA expression of LC3 and protein expression of LC3II/LC3I were higher in the SP group than in the MP group, indicating elevated autophagy under SP. Chromatin agglutination and mitochondrial damage were observed and bax/bcl2 and cytochrome C expression increased at the protein and mRNA levels in the SP and LP groups, suggesting increased apoptosis. Protein expression of dynamin-related protein 1 and mitochondrial fission factor (Mff) were highest in the SP group, suggesting elevated mitochondrial fission. Protein expression levels of adenosine triphosphate (ATP) synthase and citrate synthase were lower in the LP group than in the SP and MP groups. These results indicated that autophagy and apoptosis imbalance under SP and LP conditions may have led to HG weight loss and up-regulation of mitochondrial apoptosis may have weakened mitochondrial function under LP conditions. Finally, melatonin synthesis appeared to be positively correlated with the time hamsters entered darkness.

Estradiol and estrogen receptor α in the mPOA and MeA in dwarf hamster (Phodopus campbelli) fathers

E2 and its alpha receptor (ERα) have an essential role in the regulation of maternal behavior. In dwarf hamster (Phodopus campbelli), E2 facilitates the display of paternal care, and it is possible that ERα is part of the neuroendocrine mechanisms that regulate this behavior. The aim of this study was to analyze the influence of copulation, cohabitation with the pregnant mate and the presence of the pups on paternal behavior, circulating E2 levels and the presence of ERα in the medial preoptic area (mPOA) and medial amygdala (MeA) in dwarf hamsters. Eight males were mated with intact females (IFs), 8 with tubally ligated females (TLFs) and 8 with ovariectomized females (OFs). In males mated with IFs, paternal behavior tests were performed after copulation, halfway through pregnancy and 24 h after the birth of their pups. Males mated with TLFs were subjected to paternal behavior tests at equivalent periods as the males mated with IFs. In males mated with OFs, paternal behavior tests were performed on days 1, 5 and 10 of cohabitation. After the last paternal behavior tests, blood samples were taken for quantification of E2 by radioimmunoassay (RIA), and the brains were dissected to determine ERα immunoreactivity (ir) in the mPOA and MeA. Fathers mated with IFs had higher serum E2 concentrations and more ERα-ir cells in the mPOA than those of males mated with TLFs and OFs. These results suggest that E2 and its ERα may be associated with paternity in the dwarf hamster.

Expression of Neuroectodermal Markers in Atypical Fibromas in Two Dwarf Hamsters (Phodopus spp.)

A 2-year-old male Djungarian hamster (Phodopus sungorus) and a 1-year-old male Roborovski hamster (Phodopus roborovskii) were presented with expansile subcutaneous masses. The well-demarcated, firm, grey, multilobulated nodules displayed an homogeneous, white-grey cut surface. Histological examination revealed a neoplasm of variable cellularity consisting of spindle-shaped to polygonal 'ganglion cell-like' cells with abundant, amphophilic, vacuolated cytoplasm. Immunohistochemically, the tumour cells were labelled intensely for vimentin and nestin, moderately for neuron specific enolase and weakly for melan-A. The histological and immunohistochemical findings were suggestive of an atypical fibroma with evidence of a neuroectodermal phenotype.

Reproduction and mortality rates in ecologically distinct species of murid rodents.

The trade-off between reproduction and somatic maintenance is one of the most studied concepts of modern evolutionary ecology. This theory predicts a negative relationship between maximum species longevity and total reproductive output. However, studies performed on natural animal populations have found contradictory results, probably due to the unlikelihood of wild animals gaining both maximum longevity and maximum potential fecundity. A comparison of the mortality rates and reproductive output of four ecologically distinct rodent species of Cricetidae family that were maintained in the laboratory in controlled conditions revealed the different life-history tactics of subterranean social mole voles and three related aboveground species: hydrophilic water voles, arid dwarf hamsters and steppe lemmings. Regardless of the relatively higher mortality rates at early ages in mole voles, this species has considerably higher maximum species longevity and smaller litter sizes that do not depend on calendar age, whereas in dwarf hamsters and water voles clear negative correlations between female age and litter size were detected. Steppe lemmings, as a semi-social arid species, shared some life-history tactics with both mole voles and aboveground non-social rodents.

Rediscovered after half a century: a new record of the grey dwarf hamster, Cricetulus migratorius (Mammalia: Cricetidae), in Romania

The grey dwarf hamster, Cricetulus migratorius , is the smallest hamster species in Europe, with a highly fragmented distribution in most countries in the south-eastern part of the continent. It is rarely observed, with most records provided by raptor diet studies. Here we report a new observation from extreme north-eastern Romania, based on individuals identified in the diet of owls. The records considerably extend the known geographical range to the north in Romania and these are the first observations from an urban area in the country.

Chromosome Synapsis and Recombination in Male-Sterile and Female-Fertile Interspecies Hybrids of the Dwarf Hamsters (Phodopus, Cricetidae).

Hybrid sterility is an important step in the speciation process. Hybrids between dwarf hamsters Phodopus sungorus and P. campbelli provide a good model for studies in cytological and genetic mechanisms of hybrid sterility. Previous studies in hybrids detected multiple abnormalities of spermatogenesis and a high frequency of dissociation between the X and Y chromosomes at the meiotic prophase. In this study, we found that the autosomes of the hybrid males and females underwent paring and recombination as normally as their parental forms did. The male hybrids showed a significantly higher frequency of asynapsis and recombination failure between the heterochromatic arms of the X and Y chromosomes than the males of the parental species. Female hybrids as well as the females of the parental species demonstrated a high incidence of centromere misalignment at the XX bivalent and partial asynapsis of the ends of its heterochromatic arms. In all three karyotypes, recombination was completely suppressed in the heterochromatic arm of the X chromosome, where the pseudoautosomal region is located. We propose that this recombination pattern speeds up divergence of the X- and Y-linked pseudoautosomal regions between the parental species and results in their incompatibility in the male hybrids.

Cüce Hamsterlerin (Phodopus roborovskii) Genital Dokularında Androjen Reseptör Lokalizasyonu

Androgens perform the their effects on target tissues mainly through the androgen receptor (AR). In this study, AR localization was investigated in female and male dwarf hamsters genital tissues. In the present study, 6 female and 6 male animals were used. After anesthesia, the tissues to be worked were quickly removed from the body and fixed in 10% buffered neutral formalin, and embedded in paraffin. Sections were stained after microwave antigen retrieval for immunohistochemistry. Although AR positive immunostaining was observed only in cell nuclei in testis, caput epididymis, prostate gland and vesicle seminalis tissues, it was observed in cytoplasm or nucleus of the cells in the ovarium and oviduct tissues. AR localization in dwarf hamster male and female genital tissues was similar to other species. The presence of AR in genital tissues supports the idea that androgens are essential for these tissues.

Identification of immunohistochemical localization of irisin in the dwarf hamster (Phodopus roborovskii) tissues.

Irisin is mainly secreted by heart and skeletal muscle cells. It is an exercise-induced protein that converts white adipose tissue to brown. Increased irisin expression was lead to weight loss and improved glucose tolerance. We investigated irisin immunoreactivity in various tissues of the dwarf hamsters (Phodopus roborovskii). Tissues were processed, embedded in paraffin, sectioned at 5μm and stained immunohistochemically for irisin. In the retina, irisin was found almost all layers, except outer nuclear layer. Also, irisin immunoreactivity was observed in the skin, cornea, striated muscle, parotid gland, tongue, oesophagus, stomach and small intestine. The findings from this study support the notion that skeletal muscle is not the primary source of irisin.

Molecular phylogenetics and taxonomy of dwarf hamsters CricetulusMilne-Edwards, 1867 (Cricetidae, Rodentia): description of a new genus and reinstatement of another.

The taxonomy of the genus Cricetulus has been controversial. The phylogenetic relationships both within the genus and among Cricetulus lineages and other genera were examined using a set of five nuclear and two mitochondrial genes. The results demonstrate that Cricetulus in its current treatment is a polyphyletic assemblage because the subgenus Urocricetus is phylogenetically unrelated to all other Cricetulus and is a distant sister group to Phodopus. The grey hamster (C. migratorius) proved to be closer to Cricetus and Allocricetulus than to Cricetulus proper, which includes C. barabensis C. sokolovi and C. longicaudatus. Based on these results Urocricetus is elevated to the rank of a full genus and a new genus Nothocricetulus gen.nov. is described for the grey hamster.

An increase in estradiol facilitates the onset of paternal behavior in the dwarf hamster (Phodopus campbelli)

In the dwarf hamster (Phodopus campbelli), activational effects of testosterone (T) and estradiol (E2) in the regulation of paternal behavior have been repeatedly rejected because peripheral concentrations of E2 do not change across the reproductive cycle of males. Further, castration no affected paternal behavior despite that both T and E2 concentrations decreased significantly. However, the role of these hormones has not been evaluated in models of castration and hormonal replacement in virgin males. Here, we analysed the effects of E2 and T in paternal behavior in virgin male dwarf hamster (Phodopus campbelli). Thirty paternal (PAT) males were bilaterally castrated; of them, 10 were implanted with T, 10 with E2 and 10 males received no treatment. Other 10 PAT males underwent sham-castration. Seventeen aggressive (AGG) males were also bilaterally castrated; of these, 10 AGG received E2 replacement, 7 were not treated. Other 7 AGG males were submitted to sham-castration. Following treatments, paternal behavior tests were conducted again. T and E2 levels in plasma were quantified by radioimmunoassay (RIA). The results showed that the treatments did not affect the paternal behavior of males that were initially paternal. Neither castration nor sham-castration surgery affected the behavior of AGG males. However, when these males were treated with E2 and the concentrations of this hormone increase significantly they became paternal. Our data suggest that an increase in E2 levels shifted infanticidal behavior to paternal behavior in dwarf hamster.

The importance of genetic tools when studying the distribution of rare and elusive species illustrated by the Kam dwarf hamster

Detailed information on the distribution and abundance of animals is often difficult to establish for rare and elusive species. Here we report on genetic analyses confirming the presence of the Kam dwarf hamster 500 km north of its known distribution in China where it was earlier thought to be endemic. Our finding was made during a study on disease ecology in southern Mongolia and illustrates the benefit of genetic approaches when studying rare and elusive species or species that are either difficult to identify or do not elicit public or scientific attention. We suggest that larger ranges than currently known may be a common pattern for a number of rare and elusive species because of ineffective survey methods and lack of sampling effort.

Reproduction, ageing, and longevity in two species of laboratory rodents with different life histories.

Social subterranean rodents of the Bathyergidae family are known to have extended longevity and some signs of negligible senescence, although the manifestation of these traits depends on the reproductive status of individuals. Such enormous life history peculiarities are usually explained by the specificity of a subterranean way of life. If so, all subterranean rodents, regardless of their taxonomic position, are expected to have higher maximum lifespans and shorter senescence periods than the related above-ground species. In this study we compared the mortality rates and age-related reproductive activity and physical conditions in two sympatric rodents of the Cricetidae family: subterranean mole voles and above-ground dwarf hamsters. Mole voles have a maximum lifespan that is as high as two times the maximum lifespan of the dwarf hamsters; however, only a few mole voles outlasted the maximum lifespan of dwarf hamsters. Dwarf hamsters were generally more fecund than mole voles, which manifests both in a higher number of litters and larger litter sizes. Neither species demonstrated a significant age-related decline in litter size or muscle strength, although there were negative trends for dwarf hamsters. We conclude that some evidence of extended longevity and slow ageing do occur in mole voles, but due to the relatively short "subterranean" phylogenetic history of the species, this evidence is not as pronounced as in the social species of Bathyergidae family.

Karyotype Evolution and Phylogenetic Relationships of Cricetulus sokolovi Orlov et Malygin 1988 (Cricetidae, Rodentia) Inferred from Chromosomal Painting and Molecular Data

Sokolov's dwarf hamster (Cricetulus sokolovi) is the least studied representative of the striped hamsters (Cricetulus barabensis species group), the taxonomy of which remains controversial. The species was described based on chromosome morphology, but neither the details of the karyotype nor the phylogenetic relationships with other Cricetulus are known. In the present study, the karyotype of C. sokolovi was examined using cross-species chromosome painting. Molecular and cytogenetic data were employed to determine the phylogenetic position of Sokolov's hamster and to analyze the potential pathways of chromosome evolution in Cricetulus. Both the chromosome and molecular data support the species status of Sokolov's hamster. Phylogenetic analysis of the CYTB data placed C. sokolovi as sister to all other striped hamsters (sequence divergence of 8.1%). FISH data revealed that the karyotype of C. sokolovi is highly rearranged, with the most parsimonious scenario of its origin implying at least 4 robertsonian events and a centromere shift. Comparative cytogenetic data on Cricetinae suggest that their evolutionary history includes both periods of chromosomal conservatism and episodes of rapid chromosomal change.

Adult wheel access interaction with activity and boldness personality in Siberian dwarf hamsters (Phodopus sungorus)

Individual animal personalities interact with environmental conditions to generate differences in behavior, a phenomenon of growing interest for understanding the effects of environmental enrichment on captive animals. Wheels are common environmental enrichment for laboratory rodents, but studies conflict on how this influences behavior, and interaction of wheels with individual personalities has rarely been examined. We examined whether wheel access altered personality profiles in adult Siberian dwarf hamsters. We assayed animals in a tunnel maze twice for baseline personality, then again at two and at seven weeks after the experimental group was provisioned with wheels in their home cages. Linear mixed model selection was used to assess changes in behavior over time and across environmental gradient of wheel exposure. While animals showed consistent inter-individual differences in activity, activity personality did not change upon exposure to a wheel. Boldness also varies among individuals, and there is evidence for female boldness scores converging after wheel exposure, that is, opposite shifts in behavior by high and low boldness individuals, although sample size is too small for the mixed model results to be robust. In general, Siberian dwarf hamsters appear to show low behavioral plasticity, particularly in general activity, in response to running wheels.

Genomic imprinting, disrupted placental expression, and speciation.

The importance of regulatory incompatibilities to the early stages of speciation remains unclear. Hybrid mammals often show extreme parent-of-origin growth effects that are thought to be a consequence of disrupted genetic imprinting (parent-specific epigenetic gene silencing) during early development. Here, we test the long-standing hypothesis that abnormal hybrid growth reflects disrupted gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in dosage imbalances between paternal growth factors and maternal growth repressors. We analyzed placental gene expression in reciprocal dwarf hamster hybrids that show extreme parent-of-origin growth effects relative to their parental species. In massively enlarged hybrid placentas, we observed both extensive transgressive expression of growth-related genes and biallelic expression of many genes that were paternally silenced in normal sized hybrids. However, the apparent widespread disruption of paternal silencing was coupled with reduced gene expression levels overall. These patterns are contrary to the predictions of the LOI model and indicate that hybrid misexpression of dosage-sensitive genes is caused by other regulatory mechanisms in this system. Collectively, our results support a central role for disrupted gene expression and imprinting in the evolution of mammalian hybrid inviability, but call into question the generality of the widely invoked LOI model.

Females choose gentle, but not healthy or macho males in Campbell dwarf hamsters (Phodopus campbelli Thomas 1905).

Androgen-dependent male sexual traits (STs) as well as immunocompetence are theoretically assumed to be key indicators of a male’s quality for the mate-choosing female. We studied mate choice by sexually motivated (SM) females of Campbell’s dwarf hamsters. Females chose between 2 tethered male siblings that differed in expression of STs. Males were unrelated to the female and able to contact and copulate with her. In both males, we measured sex-related morphology of body mass, mid-ventral specific skin gland, ano-genital distance, and external testicular diameter. We also estimated levels of blood testosterone and cortisol, specific T- and B-cell immune responses to antigens, as well as aggressive and sexual dominance in sibling males through additional encounter experiments with another SM female (male sibs could freely compete for the female). We found that SM females chose a partner among 2 male sibs and spent over 80% of their time on average with the preferred male compared with the non-preferred one. Her choice was not associated with the first visit of the chosen male, with a higher expression of sex-related traits, higher levels of blood testosterone, or with aggressive dominance. The choice was not associated with the intensity of T-cell immune response to phitohemagglutinin (PHA). Instead there was a tendency for a negative relationship with the expression of STs and B-cell response to the antigen challenge. The only character that unambiguously influenced female choice was the non-aggressive male to female grooming during sexual contact. There was no difference in breeding success between preferred and non-preferred males paired with virgin females.

Resting Metabolic Rate Is Positively Correlated with Parental Care Behavior in a Dwarf Hamster.

Endotherms maintain high and constant body temperatures through the production and maintenance of metabolic heat. Defining the evolutionary history of these thermal adaptations and the selective factors responsible for the evolution of endothermy despite its high metabolic costs have been elusive and controversial topics in evolutionary biology. In this sense, several models have been proposed to explain the evolution of endothermy. Among them, the parental care model explains the increase in resting metabolic rate (RMR) by the action of natural selection favoring parental care. Thus, a positive relationship between parental care behavior and RMR is predicted. However, there appears to be no or little previous work experimentally testing this relationship. In the study presented here, RMR was increased through l-tyrosine injections and parental care behavior was measured. This treatment allowed us to test the relationship between RMR level and parental care behavior in a dwarf hamster. It was found that increased RMR enhanced male parental care. Specifically, male latency time, or the time until contacting and picking up their pups, decreased when RMR increased. This study demonstrates the positive relationship between RMR and the allocation of resources to parental care. This study supports the main assumption of Kotejas's parental care model and accepts Koteja's proposed explanation for the evolution of endothermy as a plausible hypothesis.