Allelic profile at 37 biochemical loci of two inbred strains of the house mouse derived from wild Mus musculus musculus

Two newly established inbred strains derived from Mus musculus musculus, designated PWD/Ph (F29) and PWK/Ph (F33), were examined for their alleles at 37 biochemical loci located on 12 different chromosomes. The allelic pattern showed characteristic differences from those observed in common inbred strains. The genetic distance D between PWK/Ph and PWD/Ph was 0.027, whereas the corresponding values for the genetic distances between PWK/Ph and C57BL/6J, DBA/2J, BALB/cJ and SWR/J were 0.777, 0.721, 0.721 and 0.838 respectively. New allozymes are described as being controlled by the loci Es-23, Pre-2 and Tam-1. The genetic relationship to M.m.molossinus is indicated by identical alleles at six other loci (Es-2, Es-9, Es-10, Es-11, Es-18 and Es-22).     

Single alternation with water reward:effects of sodium amobarbital on two strains of rats selectively bred for high and low emotionality.

The action of sodium amobarbital is studied during the patterning effect in rats selectively bred for low and high emotionality. The drug disrupts patterned running in the goal section of the alley in Maudsley non-reactive but not in Maudsley reactive rats for the last five trial-pairs. Sodium amobarbital also affects the behavior of these strains in a differential manner, in start and run sections, during the first trial-pair. The results show that a function-related physiological change has taken place in the Maudsley strains of rats.     

Variable responses to high density of female Mus musculus: A merger of two population regulation hypotheses

Summary Grouping of female Mus musculus resulted in an increase in mean estrous cycle length from 4 to 12 days, yet some short cycles were still observed. Short cycles were attributed to certain females who consistently maintained a short cycling pattern as well as females who exhibited both short and long cycles. Upon breeding, females that continued to show a short cycle when grouped produced and weaned more young than females with suppressed cycles. No differences in mean weaning weight or sex ratio of the litters was observed. The ecological and evolutionary implications of these findings are discussed.     

Alcohol withdrawal reactions in mouse strains selectively bred for long or short sleep times.

Two lines of mice that differ in their sensitivity to acute hypnotic effects of ethanol were tested for alcohol withdrawal reactions after a standard 3-day exposure to ethanol. The “long-sleep” strain showed a much milder withdrawal reaction than did the “short-sleep” strain. The two strains did not differ in sensitivity to convulsions elicited by pentylenetetrazol. Sleep times and withdrawal reactions did not correlate in individual mice of the genetically heterogeneous stock from which the two lines were derived.     

Metabolism of apoprotein B in selectively bred baboons with low and high levels of low density lipoproteins

Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) apoprotein (apo)-B turnover rates were measured simultaneously by injecting 131I-labeled VLDL and 125I-labeled LDL into fasting baboons (Papio sp.) selectively bred for high serum cholesterol levels and having either low or high LDL levels. The radioactivities in VLDL, intermediate density lipoprotein (IDL), LDL apoB, and urine were measured at intervals between 5 min and 6 days. Kinetic parameters for apoB were calculated in each baboon fed a chow diet or a high cholesterol, high fat diet (HCHF). VLDL apoB residence times were similar in the two groups of animals fed chow; they were increased by HCHF feeding in high LDL animals, but not in low LDL animals. Production rates of VLDL apoB were decreased by the HCHF diet in both high and low LDL animals. Most of the radioactivity from VLDL apoB was transferred to IDL. However, a greater proportion of radioactivity was removed directly from IDL apoB in low LDL animals than in high LDL animals, and only about one-third appeared in LDL. In high LDL animals, a greater proportion of this radioactivity was converted to LDL (61.4 +/- 7.2% in chow-fed animals and 49.2 +/- 10.9% in animals fed the HCHF diet; mean +/- SEM, n = 5). Production rates for LDL apoB were higher in high LDL animals than those in low LDL animals on both diets. The HCHF diet increased residence times of LDL apoB without changing production rates in both groups. VLDL apoB production was not sufficient to account for LDL apoB production in high LDL animals, a finding that suggested that a large amount of LDL apoB was derived from a source other than VLDL apoB in these animals.     

Biochemical markers of three strains derived from Japanese wild mouse (Mus musculus molossinus)

Twenty-eight biochemical markers were examined in three strains (Mol-A, Mol-N and Mol-T) derived from the Japanese wild mouse, Mus musculus molossinus, as well as five laboratory strains, Mus musculus musculus. The Mol strains showed specific alleles at as many as 12 loci. These findings emphasize that the Mol strains have significance in future genetic and developmental studies.     

Differences in the capacity of male odours to affect investigatory behaviour and different urinary marking patterns in two strains of mice,selectively bred for high and low aggressiveness.

The investigatory behaviour of male and female mice on sawdust soiled by male mice with different levels of aggressiveness was studied in two experiments. To investigate whether high and low aggressive males show different urinary marking patterns, a third experiment was set up. The strains TA(Turku Aggressive) and TNA (Turku Nonaggressive) have been developed by selective breeding. The TA-soiled bedding discouraged investigation by male mice, while females avoided TNA-soiled areas. Also the urine marking patterns differed between the high aggressive TA and low aggressive TNA males. The results indicate that the urine marking behaviour and the odour communication system in the TA and TNA males correlate with their hereditarily determined disposition for aggressive behaviour.     

Temporal differentiation in two strains of small rodents: a wood mouse (Apodemus sylvaticus) and an albino mouse (Mus musculus OF1)

Wood mice (Apodemus sylvaticus) and OF1 albino mice (Mus musculus) were compared over durations ranging from 0.5 to 7 s, using the differential reinforcement of response duration schedule (DRRD) and a 'platform' response, i.e. staying on a small platform for a specified criterion duration to be reinforced. Species-related differences were found for mean response durations, efficiency and the number of trials needed to reach a preset performance criterion. Coefficients of variation of response durations did not differ. Overall, OF1 mice needed more trials than wood mice to reach a temporal criterion. However, over 3-7 s, data from both strains almost fitted the behavioral assumptions of Scalar Timing theory. Performance of mongolian gerbils (Meriones unguiculatus) trained in a similar setting was shown for visual comparison.     

Saturation mutagenesis for dominant eye morphological defects in the mouse Mus musculus

We have summarized our extensive series of mutagenesis experiments to isolate dominant mutations in the mouse that express eye morphological defects. Thirty-two experimental groups in which parental mice were exposed to chemical mutagens or irradiation and a historical control group of the laboratory are presented. The largest series of experiments included parental exposure to ethylnitrosourea or irradiation. A total of 203 dominant mutants were confirmed among 456,890 offspring screened, which represents one of the largest collections of mutations in the mouse affecting one organ following a systematic screen of offspring of mutagenized animals. The largest group of mutations (92) was recovered in offspring of parental mice exposed to ethylnitrosourea. The second largest group of mutations (62) was recovered in irradiation experiments. Fifty-six mutations recovered in ethylnitrosourea experiments have been mapped to 22 loci. The affected genes have been identified for a number of the recovered mutations including Cryga, Crygb, Cgyge, Pax6, Pax2, Mitf, Lim2, and Cx50. On the basis of our experiences, a number of considerations when undertaking such screens are discussed, including a) choice of mutagen, b) experimental design, and c) the criteria for such experiments to ensure that mutations at novel loci will be recovered. Received: 16 December 1999 / Accepted: 16 December 1999     

The mitochondrial genome sequence of Mus terricolor: comparison with Mus musculus domesticus and implications for xenomitochondrial mouse modeling

Knowledge of the mitochondrial DNA (mtDNA) sequence of divergent murine species is critical from both a phylogenetic perspective and in understanding nuclear-mitochondrial interactions, particularly as the latter influences our xenocybrid models of mitochondrial disease. To this end, the sequence of the mitochondrial genome of the murine species Mus terricolor (formerly Mus dunni) is reported and compared with the published sequence for the common laboratory mouse Mus musculus domesticus strain C57BL/6J. These species are of interest because xenomitochondrial cybrid mice were created that harbor M. terricolor mtDNA in a M. m. domesticus nuclear background. Although the total of 1763 nucleotide substitutions represents striking heterogeneity, the majority of these are silent, leading to highly conserved protein sequences with only 159 amino acid differences. Moreover, 58% of these amino acid differences represented conservative substitutions. All of the tRNA genes and rRNA genes have homology of 91% or greater. The control region shows the greatest heterogeneity, as expected, with 85% homology overall. Regions of 100% homology were found for Conserved Sequence Block I, Conserved Sequence Block III and the L-strand origin of replication. Complex I genes showed the greatest degree of difference among protein-coding genes with amino acid homology of 91-97% among the seven mitochondrial genes. Complexes III and IV genes show high homology ranging from 98-100%. From these data, complex I differences appear most critical for the viability of M. m. domesticus: M. terricolor cybrids. Moreover, the sequence information reported here should be useful in identifying critical regions for mitochondrial transfer between species, for furthering the understanding of mitochondrial dynamics and pathology in transmitochondrial organisms, and for the study of Mus genus origins.     

Response to cecropia cocoons of Mus musculus and two species of Peromyscus

Summary In rural areas cocoons of overwintering Hyalophora cecropia spum close to the ground are opened and the pupae eaten by small mammals, but in urban areas, where cecropia populations are much larger, the cocoons are almost never opened by mammals. Peromyscus leucopus noveboracensis and P. maniculatus bairdii are abundant in rural areas, but are largely replaced by Mus musculus in urban areas. In laboratory experiments P. l. noveboracensis invariably opened cecropia cocoons and ate the pupae. P. m. bairdii were slower to open cecropia cocoons and two of twelve did not open one at all. M. musculus, on the other hand, never opened cecropia cocoons although they gnawed the silk and ate uncovered pupae. Cocoons opened in the laboratory by the two species of Peromyscus cannot be distinguished from each other or from cocoons opened in the field.Part of the Ph. D. dissertation presented by the first author to the Department of Entomology, University of Illinois. This investigation was supported in part by PHS Training Grant no. 2-T01-GM 01076 from General Medical Sciences.     

Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination

In the early stages of reproductive isolation, genomic regions of reduced recombination are expected to show greater levels of differentiation, either because gene flow between species is reduced in these regions or because the effects of selection at linked sites within species are enhanced in these regions. Here, we study the patterns of DNA sequence variation at 27 autosomal loci among populations of Mus musculus musculus, M. m. domesticus, and M. m. castaneus, three subspecies of house mice with collinear genomes. We found that some loci exhibit considerable shared variation among subspecies, while others exhibit fixed differences. We used an isolation-with-gene-flow model to estimate divergence times and effective population sizes (N(e) ) and to disentangle ancestral variation from gene flow. Estimates of divergence time indicate that all three subspecies diverged from one another within a very short period of time approximately 350,000 years ago. Overall, N(e) for each subspecies was associated with the degree of genetic differentiation: M. m. musculus had the smallest N(e) and the greatest proportion of monophyletic gene genealogies, while M. m. castaneus had the largest N(e) and the smallest proportion of monophyletic gene genealogies. M. m. domesticus and M. m. musculus were more differentiated from each other than either were from M. m. castaneus, consistent with greater reproductive isolation between M. m. domesticus and M. m. musculus. F(ST) was significantly greater at loci experiencing low recombination rates compared to loci experiencing high recombination rates in comparisons between M. m. castaneus and M. m. musculus or M. m. domesticus. These results provide evidence that genomic regions with less recombination show greater differentiation, even in the absence of chromosomal rearrangements.     

Cardiac beta-receptor variation in rat strains selectively bred for differences in susceptibility to stress

The radioligand 3H-DHA was used to estimate the density and affinity of cardiac beta-receptors in rat strains selectively bred for differences in response to stress. Maudsley Reactive rats selected for heightened reactivity to stress had a greater density of beta-adrenergic binding in cardiac membranes than rats of two genetically distinct Maudsley Non-Reactive strains selected for decreased reactivity to stress, and compared with one of these Non-Reactive strains the MNR/Har, increased affinity for 3H-DHA. Together with previous findings the present results demonstrate a negative correlation between estimates of basal sympathetic activity on the on hand, and post-synaptic beta-receptors in heart on the other, that are consistent with the notion that these receptor alterations have occurred as a result of long-term differences in pre-synaptic release of transmitter. The Maudsley strains may, therefore, provide a useful model for the study of beta-adrenergic receptors as a physiological locus for regulation of end-target responsiveness to sympathetic stimulation.     

Leptin levels and body composition of mice selectively bred for high voluntary locomotor activity

Selective breeding produced four replicate lines of high-runner (HR) mice that run on wheels for approximately 2.7 times more revolutions per day than four unselected control lines. Previous studies found that HR mice of both sexes have lower body fat (isotope dilution at 15 wk of age) and that males (females not studied) have smaller retroperitoneal fat pads (17 wk). HR mice also exhibit elevated plasma corticosterone and insulin-stimulated glucose uptake by some hindlimb muscles but apparently do not differ in circulating insulin or glucose levels (males at 18 wk). Given their lower body fat and higher activity levels, we hypothesized that HR mice would have lower circulating leptin levels than controls. Female mice were given wheel access for 6 d at 7 wk of age, as part of the routine wheel testing for the selective breeding protocol, and then were killed after one additional week without wheels to reduce possible acute effects of activity on leptin. As hypothesized, serum leptin levels were significantly lower in HR mice. ANCOVA indicated that leptin was strongly positively correlated with both total body fat (measured by ether extraction) and body mass change from weaning, but HR mice still had significantly lower adjusted leptin levels (ANCOVA). Within HR lines but not within control lines, individual variation in leptin levels was negatively correlated with amount or speed of wheel running measured a week before being killed. Growth from weaning to euthanasia and body dry mass were lower in HR mice than in controls, but absolute dry masses of the ventricles, liver, gut, and uterus plus ovaries did not significantly differ, nor did percentage of the total dry mass as fat. HR mice offer a novel model for studying the causes and consequences of physiologically relevant variations in serum leptin.     

Contractile abilities of normal and "mini" triceps surae muscles from mice (Mus domesticus) selectively bred for high voluntary wheel running.

As reported previously, artificial selection of house mice caused a 2.7-fold increase in voluntary wheel running of four replicate selected lines compared with four random-bred control lines. Two of the selected lines developed a high incidence of a small-muscle phenotype ("mini muscles") in the plantar flexor group of the hindlimb, which apparently results from a simple Mendelian recessive allele. At generations 36-38, we measured wheel running and key contractile characteristics of soleus and medial gastrocnemius muscles from normal and mini muscles in mice from these selected lines. Mice with mini muscles ran faster and a greater distance per day than normal individuals but not longer. As expected, in mini-muscle mice the medial and lateral gastrocnemius muscles were approximately 54 and 45% the mass of normal muscles, respectively, but the plantaris muscles were not different in mass and soleus muscles were actually 30% larger. In spite of the increased mass, contractile characteristics of the soleus were unchanged in any notable way between mini and normal mice. However, medial gastrocnemius muscles in mini mice were changed markedly toward a slower phenotype, having slower twitches; demonstrated a more curved force-velocity relationship; produced about half the mass-specific isotonic power, 20-50% of the mass-specific cyclic work and power (only 10-25% the absolute power if the loss in mass is considered); and fatigued at about half the rate of normal muscles. These changes would promote increased, aerobically supported running activity but may compromise activities that require high power, such as sprinting.     

Action of two pyrazine-containing chemosignals on cells of bone marrow and testes in male house mouse Mus musculus L

Evolutionary conservative chemosignal 2,5-dimethylpyrazin that is pheromone in female mice has been shown to increase frequency of mitotic aberrations analyzed with aid of metaphasic and ana-telophasic analysis in bone marrow cells. Replacement of one of methyl radicals in the pheromone molecule by the carboxyl radical reveals specificity of action of the used derivative: the frequency of disturbances revealed only by the ana-telophasic analysis increases, whereas by the metaphasic analysis, no induction of disturbance is detected. In the sperm head abnormality test there is shown a rise of the anomalies by both compounds. Possible mechanisms of specific action of the tested substances on stability of genetic apparatus of the bone marrow dividing cells in the house mouse are discussed.