Laboratory Mammals Research Articles

Immunolocalization of Aquaporin Water Channels in the Domestic Cat Male Genital Tract

Four different aquaporins (AQP1, 2, 5 and 9), integral membrane water channels that facilitate rapid passive movement of water, were immuno-localized in the excurrent ducts collected from sexually mature cats during orchiectomy. Aquaporins 1, 2 and 9, were immuno-localized at distinct levels, whereas AQP5 was undetectable all along the feline genital tract. No immunoreactivity was present at the level of the rete testis with any of the antibodies tested. In the efferent ducts, AQP1-immunoreactivity was strongly evidenced at the apical surface of the non-ciliated cells, and AQP9-immunoreactivity was shown at the periphery of both ciliated and non-ciliated cells. Aquaporins 2 was absent in the caput epididymidis, either in the efferent ducts or in the epididymal duct. Otherwise, AQP2 was increasingly localized at the adluminal surface of principal cells from the corpus to the cauda epididymidis and more weakly in the vas deferens epithelium. The supranuclear zone of the epididymal principal cells was AQP9-immunoreactive throughout the duct, with the exclusion of the vacuolated sub-region of the caput and with higher reaction intensity in the cauda region. AQP1 was present in the blood vessels all along the genital tract. AQP1 was expressed also in the smooth muscle layer of the vas deferens. The tested AQP molecules showed a different expression pattern in comparison with laboratory mammals, primates and the dog, unique other carnivore species studied to date. The present information is possibly useful in regard to the regional morphology of the feline epididymis and correlated functions, which are still a matter of debate.

Treating chronic arsenic toxicity with high selenium lentil diets

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans.

Methylmercury egg injections: Part 2—Pathology, neurochemistry, and behavior in the avian embryo and hatchling

Methylmercury (MeHg) is a toxic metal that has been frequently linked to neurochemical alterations, brain lesions, neurobehavioral changes, and reproductive impairments in wild and captive birds. Much less is known about the effects of MeHg on the developing avian brain and resulting effects on hatchling behavior. The objective of this work was to use air cell injection studies to investigate the effect of in ovo MeHg exposure on brain pathology and four neurochemical biomarkers (N-methyl-d-aspartate (NMDA) receptor, γ-aminobutyric acid (GABA) receptor, glutamine synthetase (GS) and glutamic acid decarboxylase (GAD)) that have previously been studied in wild birds, and on hatchling righting response, balance, and startle response. In a series of six studies, we exposed white leghorn chicken and Japanese quail embryos to methylmercury chloride (MeHgCl) (range: 0–6.4μg/g egg) via egg injection on embryonic day (ED) 0 and measured receptor levels and enzyme activity at different stages of embryonic (days 11, 14, and 19 in chicken; day 15 in quail) and hatchling (day 1 and day 7) development, and in whole brain or discrete brain regions (cerebrum, cerebellum, optic lobe). We assessed neurobehaviors on post hatch (PH) days 1 and 7. Despite accumulating relatively high levels of Hg in the brain, embryos and hatchlings did not consistently display neurochemical changes consistent with those seen in wild birds and laboratory mammals. Hatchlings also did not demonstrate behavioral alterations. Pathology did not indicate a difference in occurrence and types of lesions between control and dosed birds. These findings suggest that in ovo MeHg exposure alone may not be responsible for neurological impacts in bird. This work draws attention to factors, such as age and species, that may influence responses to MeHg in birds.

Engineered Deafness Reveals That Mouse Courtship Vocalizations Do Not Require Auditory Experience

Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, vocal learning has yet to be well established for a laboratory mammal. Mice are potentially an excellent model organism for studying mechanisms underlying vocal communication. Mice vocalize in different social contexts, yet whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship vocalizations emitted by chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair cells were absent and by P16 all inner and outer hair cells were absent in DTR mice. These mice did not show any auditory brainstem responses as adults. Wild-type littermates, also treated with DT at P2, had normal hair cells and normal auditory brainstem responses. We compared the temporal structure of vocalization bouts, the types of vocalizations, the patterns of syllables, and the acoustic features of each syllable type emitted by hearing and deaf males in the presence of a female. We found that almost all of the vocalization features we examined were similar in hearing and deaf animals. These findings indicate that mice do not need auditory experience during development to produce normal ultrasonic vocalizations in adulthood. We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning.

An experimental proposal for low order laboratory animals’ extension of metabolic life

Essential bibliography, with therein references included, is presented owing to the contribution of the author groups to Mitochondrial Filamentation, which is a new emerging field of physiological energy metabolism. These studies provide the first seed concept for trials to extend the metabolic life, for a few days, in low order laboratory mammals killed by electrocution, as a first type of accidental death. It is proposed, essentially, to cool out the corpses very soon after death at 12oC-14oC and take advantage of the effect super magnetism to counteract the force of gravity to install a net recurrent cycle of oxygen consumption and oxygen production by filamented mitochondria in all the organism tissues. Once the cause of death had been corrected adequately, it is possible to try the reanimation to experience the full life of the corpse with highly sophisticated methodology.

Database of Radiogenic Cancer in Experimental Animals Exposed to Low Doses of Ionizing Radiation

For decades, there have been debates regarding the nature of the relationship between exposure to low doses of ionizing radiation and cancer risk. Under the linear no-threshold hypothesis, which serves as a theoretical basis for current radiation protection standards, the risk of cancer at low levels of exposure is presumed to be directly proportional to dose. Opponents of this hypothesis claim that there are threshold doses for radiation carcinogenesis, or even a reduction in cancer risk at low doses (a phenomenon referred to as “radiation hormesis”). Epidemiological, animal, molecular, and cellular studies were conducted to resolve this controversy, although each of these study types has its strengths and limitations. Although the results of animal experiments are not directly applicable to humans, data can substantially add to our knowledge on the form of relationship between radiation dose and cancer risk in a wide range of doses. Laboratory animals are a homogeneous population with little biological variability; animal experiments are conducted under controlled conditions with good estimates of radiation doses. In order to address the question of whether or not the dose-response curve for radiation carcinogens is linear at low doses, a comprehensive database of animal carcinogenesis experiments was assembled involving exposure to different types of ionizing gradation. The database includes virtually all publicly accessible data on the induction of radiogenic cancer in laboratory mammals. This review provides a descriptive overview of the experiments included in the database, along with a qualitative assessment of the shape of the dose-response relationship for radiation carcinogenesis at low doses in experimental animals.

Age‐related variation in immunity in a wild mammal population

SummaryAge-related changes in immunity are well documented in humans and laboratory mammals. Using blood samples collected from wild Soay sheep, we show that pronounced differences in T-cell subsets and inflammatory markers amongst age classes are also evident under natural conditions. These shifts parallel those observed in mammals experiencing protected environments. We found progressive declines in the proportion of naïve CD4 T cells with age, a precipitous drop in γδ T cells after the second year of life and an increase in acute phase protein levels amongst geriatric sheep. Our findings suggest immune aging patterns observed in laboratory and domestic mammals may generalize to more complex, challenging environments and could have fitness costs under natural conditions.

Terminology of developmental abnormalities in common laboratory mammals (version 2)

From: Birth Defects Research (Part B) 86:227–327 (2009). At the time that the Version 2 terminology manuscript was published, the authors invited all users to submit corrections and comments. As of the current date, only five minor corrections have been identified. These are listed as follows. There was a misspelling in the company name for Yojiro Ooshima on page 227; the corrected affiliation is: Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan. The company name for Meg Parkinson was mistakenly listed as GlaxoSmithKline Services on page 227; the correct company name is GlaxoSmithKline Pharmaceuticals. In the acknowledgements of the contributions of MARTA/MTA colleagues on page 232, the surname of Joyce Rendemonti was misspelled, and the affiliations of Connie Johnson and Joyce Rendemonti were not listed. The corrected acknowledgement for these two colleagues should read: “Connie Johnson, Joyce Rendemonti (GlaxoSmithKline Pharmaceuticals)”. In Table 3, Skeletal Abnormalities, page 292, the first entry below the table header, in the second column (which presents the first “Observation” term) incorrectly indicates “Cervical”. The correct term (which should replace “Cervical”) is “Thoracolumbar”. In Table 3, Skeletal Abnormalities, page 293, the first entry below the table header and above “Vertebra” in the first column (which presents the “Region/Organ/Structure”) incorrectly indicates “Supernumerary rib Cervical cont.”. The word “Cervical” should be deleted, and the correct term is “Supernumerary rib cont.”

Scorpion sting nephropathy.

Scorpion envenomations are ubiquitous, but nephropathy is a rare manifestation, reported mainly from the Middle East and North Africa. Rapid venom redistribution from blood, delayed excretion from the kidneys, direct toxicity of venom enzymes, cytokine release and afferent arteriolar constriction have been seen in experimental animals. Haemoglobinuria, acute tubular necrosis, interstitial nephritis and haemolytic–uraemic syndrome have been documented in human victims of scorpion envenomation. Epidemiology, venom components and toxins, effects on the laboratory mammals especially the kidneys and reports of renal failure in humans are reviewed in this article.

Retention of tritium in reference persons: a metabolic model. Derivation of parameters andapplication of the model to the general public and to workers

Tritium (3H) is a radioactive isotope of hydrogen that is ubiquitous in environmental and biologicalsystems. Following debate on the human health risk from exposure to tritium, there havebeen claims that the current biokinetic model recommended by the InternationalCommission on Radiological Protection (ICRP) may underestimate tritium doses. Anew generic model for tritium in mammals, based on energy metabolism andbody composition, together with all its input data, has been described in a recentpaper and successfully tested for farm and laboratory mammals. That modelconsiders only dietary intake of tritium and was extended to humans. This paperpresents the latest development of the human model with explicit considerationof brain energy metabolism. Model testing with human experimental data onorganically bound tritium (OBT) in urine after tritiated water (HTO) or OBTintakes is presented. Predicted absorbed doses show a moderate increase for OBTintakes compared with doses recommended by the ICRP. Infants have highertritium retention—a factor of 2 longer than the ICRP estimate. The highest tritiumconcentration is in adipose tissue, which has a very low radiobiological sensitivity. Theranges of uncertainty in retention and doses are investigated. The advantage ofthe new model is its ability to be applied to the interpretation of bioassay data.

Hypoxia and the Edema Syndrome: elucidation of a mechanism of teratogenesis

The elucidation of mechanisms and pathogenesis of birth defects is exceedingly complex. Consequently, there are few examples where the etiology of birth defects caused by a specific agent has been well described. One such example is the "Edema Syndrome" first described by Casimer Grabowski in the 1960s as a mechanism of hypoxia-induced malformations in the chick embryo. The Edema Syndrome comprised a series of events in the embryo starting with osmotic imbalances followed by edema, distention, blisters, hematomas, and hemorrhage in or near developing structures. Malformation or deformation of structures resulted from mechanical disruption or loss of blood supply. A similar etiology has since been described by others in a variety of laboratory mammals following treatment with drugs including epinephrine, hydroxyurea, cocaine, phenytoin, and potassium channel-blocking drugs. Free radical excess following transient hypoxia may be a common factor in all of these insults. Vascular disruption is also associated with a number of birth defects in humans, including limb and digit reduction defects and urogenital defects.

Strain‐dependent differences in electrogenic secretion of electrolytes across mouse colon epithelium

Mice have proven to be powerful models for the study of human physiology and pathophysiology. With the advent of techniques for genomic manipulation, the possibilities for studying inherited diseases in this convenient laboratory mammal are increasing by the day. It has been reported that when knocking out or otherwise modifying genes of interest in mice, the phenotype obtained can vary markedly depending on the genetic background of the animals used in the study. The aim of this work was to study whether the genetic background can influence the characteristics of fluid and electrolyte transepithelial transport in the distal colon of three mouse strains most in use in our and other laboratories. Ussing chamber recordings revealed that the colons of C57Bl/6J, Sv 129 and Black Swiss animals have distinctive responses to the calcium agonists carbachol and histamine that are not explained by the presence of different types of muscarinic and histaminergic receptors in these tissues. We have also found differences in the cAMP-activated, KCNMA1-channel-dependent potassium secretion between the strains. We interpret this to indicate a unique distribution of KCNMA1 channels in lower parts of the crypt of Sv 129 colonic epithelium compared with that of C57Bl/6J and Black Swiss animals. The reported differences should be taken into account when choosing the genetic background of animals to be used for genetic modification.

Development of the autonomic nervous system: A comparative view

In this review we summarize current understanding of the development of autonomic neurons in vertebrates. The mechanisms controlling the development of sympathetic and enteric neurons have been studied in considerable detail in laboratory mammals, chick and zebrafish, and there are also limited data about the development of sympathetic and enteric neurons in amphibians. Little is known about the development of parasympathetic neurons apart from the ciliary ganglion in chicks. Although there are considerable gaps in our knowledge, some of the mechanisms controlling sympathetic and enteric neuron development appear to be conserved between mammals, avians and zebrafish. For example, some of the transcriptional regulators involved in the development of sympathetic neurons are conserved between mammals, avians and zebrafish, and the requirement for Ret signalling in the development of enteric neurons is conserved between mammals (including humans), avians and zebrafish. However, there are also differences between species in the migratory pathways followed by sympathetic and enteric neuron precursors and in the requirements for some signalling pathways.

Anatomy, pathology, and physiology of the tracheobronchial tree: Emphasis on the distal airways

This article covers the airway tree with respect to anatomy, pathology, and physiology. The anatomic portion discusses various primate groups so as to help investigators understand similarities and differences between animal models. An emphasis is on distal airway findings. The pathology section focuses on the inflammatory responses that occur in proximal and distal airways. The physiologic review brings together the anatomic and pathologic components to the functional state and proposes ways to evaluate the small airways in patients with asthma.

Terminology of developmental abnormalities in common laboratory mammals (version 2)

This update (version 2) of the Terminology of developmental abnormalities in common laboratory mammals ( version 1) by Wise et al. [Wise LD, Beck SL, Beltrame D, Beyer BK, Chahoud I, Clark RL, Clark R, Druga AM, Fueston MH, Guittin P, Henwood SM, Kimmel CA, Lindstrom P, Palmer AK, Petrere JA, Solomon HM, Yasuda M, York RG. Terminology of developmental abnormalities in common laboratory mammals (version 1). Teratology 1997;55:249–92] incorporates improvements and enhancements to both content and organization of the terminology, to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops. The terminology remains organized into tables under the broad categories of external, visceral, and skeletal observations, following the manner in which data are typically collected and recorded in developmental toxicity studies. This arrangement of the tables, as well as other information provided in appendices, is intended to facilitate the process of specimen evaluation at the laboratory bench level. Only the commonly used laboratory mammals (i.e., rats, mice, rabbits) are addressed in the current terminology tables. The inclusion of other species that are used in developmental toxicity testing, such as primates, is considered outside the scope of the present update. Similarly, categorization of findings as, for example, “malformation” or “variation” remains unaddressed, in accordance with the overall principle that the focus of this document is descriptive terminology and not diagnosis/interpretation. The skeletal terms have been augmented to accommodate cartilage findings.

Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 2)

This update (Version 2) of the Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 1) incorporates improvements and enhancements to both content and organization of the terminology to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops. The terminology remains organized into tables under the broad categories of external, visceral, and skeletal observations, following the manner in which data are typically collected and recorded in developmental toxicity studies. This arrangement of the tables, as well as other information provided in appendices, is intended to facilitate the process of specimen evaluation at the laboratory bench level. Only the commonly used laboratory mammals (i.e. rats, mice, rabbits) are addressed in the current terminology tables. The inclusion of other species that are used in developmental toxicity testing, such as primates, is considered outside the scope of the present update. Similarly, categorization of findings as, for example, 'malformation' or 'variation' remains unaddressed, in accordance with the overall principle that the focus of this document is descriptive terminology and not diagnosis or interpretation. The skeletal terms have been augmented to accommodate cartilage findings.

Terminology of developmental abnormalities in common laboratory mammals (Version 2)

This update (Version 2) of the Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 1) by Wise et al. (1997) incorporates improvements and enhancements to both content and organization of the terminology, to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops. The terminology remains organized into tables under the broad categories of external, visceral, and skeletal observations, following the manner in which data are typically collected and recorded in developmental toxicity studies. This arrangement of the tables, as well as other information provided in appendices, is intended to facilitate the process of specimen evaluation at the laboratory bench level. Only the commonly used laboratory mammals (i.e., rats, mice, rabbits) are addressed in the current terminology tables. The inclusion of other species that are used in developmental toxicity testing, such as primates, is considered outside the scope of the present update. Similarly, categorization of findings as, for example, "malformation" or "variation" remains unaddressed, in accordance with the overall principle that the focus of this document is descriptive terminology and not diagnosis/interpretation. The skeletal terms have been augmented to accommodate cartilage findings.

Cardiovascular changes during daily torpor in the laboratory mouse

The laboratory mouse is a facultative daily heterotherm in that it experiences bouts of torpor under caloric restriction. Mice are the most frequently studied laboratory mammal, and often, genetically modified mice are used to investigate many physiological functions related to weight loss and caloric intake. As such, research documenting the cardiovascular changes during fasting-induced torpor in mice is warranted. In the current study, C57BL/6 mice were implanted either with EKG/temperature telemeters or blood pressure telemeters. Upon fasting and exposure to an ambient temperature (T(a)) of 19 degrees C, mice entered torpor bouts as assessed by core body temperature (T(b)). Core T(b) fell from 36.6 +/- 0.2 degrees C to a minimum of 25.9 +/- 0.9 degrees C during the fast, with a concomitant fall in heart rate from 607 +/- 12 beats per minute (bpm) to a minimum of 158 +/- 20 bpm. Below a core T(b) of 31 degrees C, heart rate fell exponentially with T(b), and the Q(10) was 2.61 +/- 0.18. Further, mice implanted with blood pressure telemeters exhibited similar heart rate and activity profiles as those implanted with EKG/temperature telemeters, and the fall in heart rate and core T(b) during entrance into torpor was paralleled by a fall in blood pressure. The minimum systolic, mean, and diastolic blood pressures of torpid mice were 62.3 +/- 10.2, 51.9 +/- 9.2, 41.0 +/- 7.5 mmHg, respectively. Torpid mice had a significantly lower heart rate (25-35%) than when euthermic at mean arterial pressures from 75 to 100 mmHg, suggesting that total peripheral resistance is elevated during torpor. These data provide new and significant insight into the cardiovascular adjustments that occur in torpid mice.

Interplay among enteric neurons, interstitial cells of Cajal, resident and not resident connective tissue cells

Interplay among enteric neurons, interstitial cells of Cajal, resident and not resident connective tissue cells

The involvement of surface sugars of mammalian spermatozoa in epididymal maturation and in vitro sperm-zona recognition: Die Beteiligung von Oberflächen-Zuckern von Säuger-Spermatozoen auf die Nebenhodenreifung und die in vitro Spermatozoen-Zona-Erkennung

The distribution of various simple sugar residues over the spermatozoa surfaces of five different mammalian species is characterized and compared. Epididymal maturation of the spermatozoa of all the five species studied exhibited an increase in the amount of N-acetyl-D-glucosamine residues over their acrosomal domains. A complete blockade of sperm-zona pellucida attachment of hamster gametes could be brought about when spermatozoa were treated previously with 0.1 M of N-acetyl-D-glucosamine. This sugar seems to be specifically involved in sperm-zona pellucida attachment in hamsters. The inter-specific cross-reactivity of gametes of laboratory mammals like rat, mouse, rabbit and hamster could, quite likely, be because of the involvement of N-acetyl-D-glucosamine as a common factor in this reaction in these animals.