Laboratory Mouse Populations Research Articles

Bacteriophage-driven emergence and expansion of Staphylococcus aureus in rodent populations.

Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species.

Development of a multiplex serological assay reveals a worldwide distribution of murine astrovirus infections in laboratory mice.

Laboratory mice play a tremendous role in biomedical research in studies on immunology, infection, cancer and therapy. In the course of standardization of mice used in animal experiments, health monitoring constitutes an important instrument towards microbiological standardization. Infections with murine astroviruses (MuAstV) were only recently discovered and are, therefore, still relatively unknown in laboratory animal science. In rodent health monitoring viral infections within a population are commonly assessed in terms of specific antibodies by serological testing, as active infection and excretion of virus is often temporary and can easily be missed. So far only ongoing infections with astroviruses can be detected by PCR. The objective of this work was the development of a sensitive and specific MuAstV multiplex serological assay with a high-throughput capability to be used in routine testing of laboratory mice. Four different MuAstV proteins were recombinantly expressed and used as antigens. The best reacting antigen, the capsid spike protein VP27, was selected and tested with a panel of 400 sera of mice from units with a known MuAstV status. Assay sensitivity and specificity resulted in 98.5% and 100%, respectively, compared to RT-PCR results. Eventually this assay was used to test 5529 serum samples in total, during routine diagnostics at the German Cancer Research Center (DKFZ) in Heidelberg between 2015 and 2017. High sero-prevalence rates of up to 98% were detected in units with open cages indicating that the virus is highly infectious and circulates within these populations virtually infecting all animals regardless of the mouse strain. In addition, data collected from 312 mice purchased from commercial breeders and from 661 mice from 58 research institutes in 15 countries worldwide allowed the conclusion that MuAstV is widespread in contemporary laboratory mouse populations.

Advantages of a Mouse Model for Human Hearing Impairment

Hearing is a major factor in human quality of life. Mouse models are important tools for discovering the genes that are responsible for genetic hearing loss, and these models often allow the processes that regulate the onset of deafness in humans to be analyzed. Thus far, in the study of hearing and deafness, at least 400 mutants with hearing impairments have been identified in laboratory mouse populations. Analysis of through a combination of genetic, morphological, and physiological studies is revealing valuable insights into the ontogenesis, morphogenesis, and function of the mammalian ear. This review discusses the advantages of the mouse models of human hearing impairment and highlights the identification of the molecules required for stereocilia development in the inner ear hair cells by analysis of various mouse mutants.

Phenotypic and Expression Analysis of a Novel Spontaneous Myosin VI Null Mutant Mouse

In humans, hearing is a major factor in quality of life. Mouse models are important tools for the discovery of genes responsible for genetic hearing loss, often enabling analysis of the processes that regulate the onset of deafness in humans. Thus far, at least 400 deafness mutants have been discovered in laboratory mouse populations and used in the study of deafness. Here we report the discovery of a new spontaneous recessive Rinshoken shaker/waltzer (rsv) mutant derived from our in-house C57BL/6J stock, which exhibits circling and/or head-tossing behaviour and complete lack of auditory brain response to any sound pressure. The hearing and balance phenotypes are associated with structural defects, in particular, disorganisation and fusion of stereocilia in the inner ear hair cells. Two sets of intersubspecific N(2) mice were generated for the positional cloning of the rsv mutation. The mutant locus was mapped to a 4.8-Mb region of chromosome 9, which contains myosin VI (Myo6), a gene responsible for deafness in humans and Snell's waltzer mutation in mice. The rsv mutant showed reduced expressions of Myo6 mRNA and MYO6 protein in the inner ear. Moreover, no immunoreactivity was observed in the cochlear and vestibular hair cells in the rsv mutant mice. We sequenced the genomic region (30,154 bp) of Myo6, including all coding exons, a non-coding exon, UTRs and the Myo6 promoter; however, no mutation was discovered in these regions. We therefore speculate that loss of MYO6 expression might cause shaker/waltzer behaviour and deafness in the rsv mutant; also, loss of MYO6 expression might be the result of mutations in an unidentified regulatory region(s) of the gene.

Genetic Variation and Population Substructure in Outbred CD-1 Mice: Implications for Genome-Wide Association Studies

Outbred laboratory mouse populations are widely used in biomedical research. Since little is known about the degree of genetic variation present in these populations, they are not widely used for genetic studies. Commercially available outbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation within CD-1 mice to investigate their suitability for genetic studies. The CD-1 mouse genome displays patterns of linkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observed among CD-1 mice obtained from different breeding facilities. Differences in genetic variation among CD-1 mice from distinct facilities were similar to genetic differences detected between closely related human populations, consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerations for the design and analysis of genetic studies in CD-1 mice.

Diagnosis of mouse hepatitis virus contamination in mouse population by using nude mice and RT-PCR

Mouse hepatitis virus (MHV) infection in laboratory mouse populations is a serious problem, because the MHV infections are known to interfere with research results. Confirmation of indirect serological detection methods by viral isolation is difficult. Reverse transcription plus polymerase chain reaction (RT-PCR) was used to test 94 mouse tissue samples from suspected naturally MHV infected mice. Positive results were only obtained from two colon samples and one mixed sample with colon and liver. The low positive rate is probably due to the virus being rapidly cleared by the MHV antibodies produced in the mouse. However, RT-PCR detection of MHV in nude mice placed in the same cages with other non-nude mice or placed in cages with used dirty bedding, showed a very high positive rate: 10 out of 12 colon samples were positive (83%), and 5 out of 10 faecal samples were positive (50%). A single-tube, single step RT-PCR method and two procedures for isolation of the viral RNA for the RT-PCR assay were also included in this article.

Role of host age and genotype in murine enterotropic coronavirus infection.

Enterotropic mouse hepatitis virus (MHV) is probably the most common form of MHV in contemporary laboratory mouse populations, but very little is known about its pathogenesis. In spite of a large volume of literature on MHV, most of these reports are related to the respiratory prototype strains of virus (1, 2). When several prototype MHV and enterotropic MHV strains were inoculated into infant mice, it became clear that different MHV strains produced two distinctly different patterns of disease: respiratory, in which virus disseminated from nasal epithelium to multiple target organs; or enterotropic, in which virus was largely restricted to intestine, with minimal dissemination (3). However, enterotropic MHV has been poorly characterized because of its fastidious and selective in vitro growth characteristics. Host age seems to significantly influence the outcome of disease in mice infected with enterotropic MHV (4–11), and host genotype may also be important in susceptibility to enterotropic MHV disease (12). These are well established factors in the pathogenesis of respiratory or polytropic MHV disease (1, 2). The present study systematically examined the relative susceptibility of inbred mice of different ages that have previously been shown to develop severe (BALB/cByJ) or mild (SJL/J) disease when inoculated oronasally with respiratory MHV-JHM (13). Pilot studies suggested that these mouse genotypes also display differential disease severity when infected with enterotropic MHV, strain Y (12).

Analysis of Dichotomous Response Data from Toxicological Experiments Involving Stable Laboratory Mouse Populations

The comparability between an analysis of variance that employs untransformed proportions and one that employs two common arcsine transforms is assessed by using preweaning mouse litter survival data from a toxicological experiment that involves stable laboratory populations. The importance of controlling for litter order, litter size and birth cohort is demonstrated. An adaptation of a nonparametric method suggested by Mantel (1963, Journal of the American Statistical Association 58, 690-700) is proposed as an alternative procedure. Although the results indicate that the nonparametric method is modestly less powerful than the parametric approach, its use is recommended when the assumptions underlying the analysis of variance are questionable. A method for plotting the temporal pattern of the effect of continuous exposure to the toxicant (DDT) on preweaning survival is also presented.

Group sequential methods for cohort and case-control studies

Long-term toxicological and epidemiological studies are often designed for continuous monitoring in order to detect valid statistical evidence of adverse health effects. Standard significance tests are not appropriate when data are periodically evaluated over the course of an investigation. Group sequential methods, however, permit repeated significance testing of periodically accumulated data while maintaining the required overall level of significance. Here we present a group sequential approach to the design and analysis of cohort and case-control studies. The method is illustrated on accumulating pre-weaning and post-weaning survival data from a toxicological/epidemiological study involving two stable laboratory mouse populations: one continuously exposed to a dietary level of 100 ppm DDT and the other nonexposed. During the 70-week course of the study, the populations were maintained at 400 by weekly replacement of dead mice with randomly selected weanlings. The accumulating post-weaning survival data are analyzed by repeated significance testing using the Mantel-Haenszel test with adjustment for confounding factors. A table is presented for a cohort study in which the average sample size required for a particular group sequential design is compared to that of the conventional fixed sample design. The table shows that a group sequential design is in general more efficient than a fixed sample plan for a cohort study.

Effects of DDT on stable laboratory mouse populations.

Four stable laboratory mouse populations were established; each contained approximately 400 mice of both sexes and all ages postweaning living in a single cage, as well as neonates caged in separate nesting boxes with their dams. Two were used to determine the effects of continuous exposure to a dietary level of 100 ppm DDT while the other two served as controls. The results indicated a significant decrease (p less than or equal to 0.05) in neonatal survival (lactation index) within 20 wk after the beginning of exposure to the toxicant in one of the exposed populations and by 30 wk in the other. This deleterious effect of the DDT continued through each succeeding generation. On the other hand, improved postweaning survival in DDT-fed mice was noted. Histological examination showed no tumors in test or control animals; other pathology was seen more frequently in control than in test animals.

Selection and cell communication as determinants of female phenotype.

As a consequence of X-chromosome inactivation, one X chromosome becomes the sole determinant of the X-specified characteristics of the cell, leading to potential cellular mosaicism in females. If there were no differences between the maternal and paternal alleles at any X-linked locus, there would be no cellular mosaicism. However, unlike the relatively homogeneous laboratory mouse populations, the human population is very heterogeneous, largely attributable to heterozygosity at many loci. Based on estimates by Harris and Hopkinson (1972), it seems certain that most women are heterozygous at one and probably more than ten X-linked loci. Therefore, with respect to her X-linked genes, the phenotype of the female is determined by the nature of her individual heterozygosity, the effect of random inactivation on the proportions of cells of the two types in each tissue, and the result of selection following inactivation.

Aggression, social pressure and asymptote in laboratory mouse populations.

Freely growing populations of BALB/cJ, C57BR/cdJ and C57BL/6J mice were maintained until after asymptote in the presence of ad libitum food and water. If aggression were an index of social pressure then aggression at asymptote should be stable. After asymptote was reached aggression increased in two of the three strains. Therefore aggression as measured here does not index social pressure. BALB/cJ populations had more aggression and fewer mice at asymptote than did populations of the other two strains. The relative aggressiveness of these three strains depends on the environment in which they are observed.

Behavioral, Pituitary, and Adrenal Correlates of Controlled Fighting (Defeat) in Mice

Previous articleNext article No AccessBehavioral, Pituitary, and Adrenal Correlates of Controlled Fighting (Defeat) in MiceF. H. Bronson, and B. E. EleftheriouF. H. Bronson Search for more articles by this author , and B. E. Eleftheriou Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Volume 38, Number 4Oct., 1965 Article DOIhttps://doi.org/10.1086/physzool.38.4.30152417 Views: 3Total views on this site Citations: 30Citations are reported from Crossref Journal History This article was published in Physiological Zoology (1928-1998), which is continued by Physiological and Biochemical Zoology (1999-present). Copyright 1965 University of ChicagoPDF download Crossref reports the following articles citing this article:Karen B. Firestone, Katrina V. Thompson, C. 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