Cytokine production by NZB, C58, and NZB X C58 recombinant inbred mice

Humans with autoimmune disease and autoimmune mouse strains such as NZB have been shown to produce reduced levels of the cytokines interleukin 1 and interleukin 2. The NZB X C58 recombinant inbred (N X 8 RI) strains exhibit certain of the autoimmune characteristics of the NZB strain. Their abilities to produce interleukin 1 and interleukin 2 have been tested. Deficiencies in the production of one or both of these cytokines were observed in the N X 8 RI strains. Decreased interleukin 2 production was not due to inability to respond to concanavalin A or allogeneic stimulation, nor to altered kinetics of the response. No correlation was observed between cytokine deficiencies and the inherited autoimmune characteristics previously studied in these strains. One especially interesting strain was N X 8 RI 16, which made high amounts of interleukin 2 but no detectable interleukin 1.     

Comparison of mouse mammary tumor virus-specific DNA in inbred, wild and Asian mice, and in tumors and normal organs from inbred mice.

The crystal and molecular structure of the dimer of variable domains of the Bence-Jones protein ROY has been determined by Patterson function search procedures, using the known structure of the protein REI. The structure has been partially refined at 3.0 Å resolution to a crystallographic R-factor value of 0.33. One of the 18 residues differentiating ROY from REI is the substitution of Tyr96 for Leu96, a substitution which makes the combining site of the ROY dimer larger. Substantial movement of Tyr49 suggests that point substitutions in the hypervariable segments may affect the conformation of neighbouring residues in the antigen-combining site, possibly producing differences in specificity larger than might otherwise be expected.     

Persistent sexual behavior in castrated, recombinant inbred mice.

In contrast to other male mice, many hybrid B6D2F1 males continue to mate after being castrated in adulthood. This persistent sexual behavior in the castrated hybrids presumably is based upon heterozygosity that might occur within individual loci or between different loci. Those possibilities were discriminated by studying BXD recombinant inbred mice. In BXD strains, individual loci are homozygous, but heterozygosity has arisen between separate loci. Males in two of six BXD strains persisted in copulating for 5 mo after being castrated. Thus, it is concluded that retention of masculine sexual behavior in castrated mice is a function of heterozygosity between loci.     

Identification of inbred strains of mice,Mus musculus. I. Genetic control of inbred strains of mice using starch gel electrophoresis

Fifteen biochemical markers were tested in 30 inbred strains of mice to control the genetic constitution of each strain. Discrepancies in pattern from Standardized Nomenclature for Inbred Strains of Mice are reported and discussed.This work was supported by Grant No. 512–2532 from the Danish Medical Research Council.     

Emotionality, exploratory behavior, and locomotion in aging inbred strains of mice.

Two inbred strains of mice, C57BL/6J and DBA/2J, ranging in age from 2 to 38 months, were tested in an open field using the free exploration method. Scores were obtained for locomotor activity, exploratory behavior and emotionality. Strain differences were observed for all three variables. Beginning at late maturity (12 months), locomotor activity decreased with increasing age. Exploratory behavior was at a low level for DBA/2J mice at all ages. For C57BL/6J mice, exploratory behavior decreased significantly between 2 and 6 months and remained stable thereafter. Emotionality remained unchanged with advancing age for both strains of mice.     

Cryptosporidium infections in inbred strains of mice.

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.     

Heterosis, sex and maternal interactions in crosses among inbred lines of mice.

All possible crosses and reciprocals were made among four inbred lines (F = 92%) developed from 12 generations of full-sib mating. All lines originated from a common outbred base population of ICR-albino mice. Data were obtained from 356 litter containing 2,734 mice to evaluate heterosis, reciprocal effects, sex effects and their interactions as they affect body weight and weight gain. Heterosis was significant for most of the postweaning traits (42- and 56-day weight and gain from 21 to 42 days). Nonadditive gene action may have included overdominance and epistasis since both reciprocal linecrosses were generally heavier than those of the better inbred lines. Although significant differences in reciprocals and inbred lines were not frequent, there were sufficient differences to indicate that lines varied in the fixation of loci during inbreeding. Sex-heterosis interactions were significant for 12 of 30 possible cases. However, eight of the 12 significant interactions occurred in crosses involving only one of the lines. The interactions were of the divergent type and arose from males exhibiting more heterosis than females. Overdominance in genes on the sex chromosomes modified by other loci (epistasis) was proposed as a possible explanation for these results. Some sex-linkage affecting growth was evident from the interaction of sex with reciprocal effects.     

Genetic analysis of cholesterol accumulation in inbred mice.

Genetic linkage analysis in the laboratory mouse identified chromosomal regions containing genes that contribute to cholesterol accumulation in the liver and plasma. Comparisons between five inbred strains of mice obtained from the Jackson Laboratory (DBA/2, AKR, C57BL/6, SJL, and 129P3) revealed a direct correlation between intestinal cholesterol absorption and susceptibility to diet-induced hypercholesterolemia. This correlation was lost in the F1 generation arising from crosses between high- and low-absorbing strains. Linkage analyses in AKxD recombinant inbred strains and 129xSJL129F1 N2 backcross mice identified four quantitative trait loci (QTL) that influenced Liver cholesterol accumulation (Lcho1-4) and one locus that affected Plasma cholesterol accumulation (Pcho1). These loci map to five chromosomes and, with one exception, are different from the seven QTL identified previously that influence intestinal cholesterol absorption. We conclude that a large number of genes affects the amount of cholesterol absorbed in the small intestine and its accumulation in the liver and plasma of inbred mice.     

Photoperiod, reproduction, and immunity in select strains of inbred mice

The purpose of this study was to determine whether decreased day lengths affect reproduction or the immune system in inbred mice. Irrespective of a nocturnal pineal melatonin rise, the signal for day length information, body and testis weights were the same in various strains 8 weeks after transfer from long to short days (16 to 8 h of light/day) compared to mice that remained in long days. Serum testosterone was unaffected by the photoperiod shift. The second goal was to determine whether the shift from long to short days influenced lymphocyte populations in spleen or blood, as well as innate and cell-mediated immune cell functions in C3H/HeN mice, an inbred strain with a robust melatonin rhythm. By flow cytometry, a stable percentage and number of B cells, T cells, and natural killer cells were identified in spleen from mice in both long and short days during the day and night. This complement of immunophenotypes in spleen suggests that equivalent functional capabilities persist in secondary lymphoid tissue of mice irrespective of day length. This was supported by findings that cytolytic activity by splenic natural killer cells (innate immunity) and antigen-induced T cell-dependent B cell antibody production (adaptive immunity) were similar in mice in long and short days. In blood, cell numbers but not helper T cell subset percentages (i.e., naive, memory, cytotoxic, or activated) were augmented in mice in short compared to long days, a consequence of increased circulating B cells. Day length differences in certain immunophenotypes in circulation may forecast photoperiod-mediated alterations in responsiveness to pathogens that are associated with a change in season. At night, the reduced proportion of cytotoxic T cells (long and short days), as well as increases in the percentage of activated T cells (long days), B cells (short days), and NK cell activity (long and short days) relative to daytime, suggests that surveillance and function by select immunophenotypes may adapt to circadian transitions even in highly inbred species. Thus, inbred mice retain capabilities for photoperiod to influence trait-specific aspects of immune cell but not reproductive function.     

Nucleotide variation in wild and inbred mice

The house mouse is a well-established model organism, particularly for studying the genetics of complex traits. However, most studies of mice use classical inbred strains, whose genomes derive from multiple species. Relatively little is known about the distribution of genetic variation among these species or how variation among strains relates to variation in the wild. We sequenced intronic regions of five X-linked loci in large samples of wild Mus domesticus and M. musculus, and we found low levels of nucleotide diversity in both species. We compared these data to published data from short portions of six X-linked and 18 autosomal loci in wild mice. We estimate that M. domesticus and M. musculus diverged <500,000 years ago. Consistent with this recent divergence, some gene genealogies were reciprocally monophyletic between these species, while others were paraphyletic or polyphyletic. In general, the X chromosome was more differentiated than the autosomes. We resequenced classical inbred strains for all 29 loci and found that inbred strains contain only a small amount of the genetic variation seen in wild mice. Notably, the X chromosome contains proportionately less variation among inbred strains than do the autosomes. Moreover, variation among inbred strains derives from differences between species as well as from differences within species, and these proportions differ in different genomic regions. Wild mice thus provide a reservoir of additional genetic variation that may be useful for mapping studies. Together these results suggest that wild mice will be a valuable complement to laboratory strains for studying the genetics of complex traits.     

Ganglioside compositions of erythrocytes from various strains of inbred mice. Ocurrence of sialosylgalactosylceramide in red blood cells of inbred mice

The gangliosides from the erythrocytes of various strains of inbred mice were analyzed. The ganglioside compositions differed in different strains and the strains could be divided into 4 types on the basis of this difference. The main ganglioside is GM4 or sialosyl galactosyl ceramide in Type 1, and unidentified ganglioside in Type 2, GM4 and GM2 in almost equal amounts in Type 3, and GM2 in Type 4.     

Serum testosterone, agonistic behavior, and dominance in inbred strains of mice

Social situations in which male mice establish dominant/subordinate relationships were utilized in an attempt to correlate circulating testosterone (T) titer with agonistic behavior. Two long-term (several months) and two short-term (3- and 5-day) situations in which dominance was verified by severity of body scarring or individual aggression scores indicated no consistent correlation of dominance with serum T levels.