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Variation in resistance to herpes simplex virus type 1 of oligodendrocytes derived from inbred strains of mice.

Primary oligodendrocyte (OL) cultures from three inbred strains of mice with known differences in resistance to herpes simplex virus type 1 (HSV-1) infection in vivo (A/J, susceptible; BALB/cByJ, moderately resistant; C57BL/6J, resistant), also display a similar pattern of resistance in vitro. The nature of the in vitro resistance at the cellular level was investigated. Virus production at different m.o.i.s indicated that the differences in HSV-1 replication are m.o.i.-dependent. Overall, virus yield from the OL cultures infected at a multiplicity of 1 increased 48 h post-infection (p.i.); no additional enhancement occurred 72 h p.i. However, the difference in the replication capacity of the three OL cultures observed at 24 h p.i. persisted at 48 and 72 h p.i. Serial electron microscopy studies on infected OL cultures derived from the different murine strains suggested that the resistance to HSV-1 infection occurs at different stages during the replicative cycle. Virus was detected at the nuclear membrane 5 min p.i. in A/J cells, but was not observed until 120 min p.i. in BALB/cByJ cells, whereas virus could not be detected at the nuclear membrane of C57BL/6J cells, even at 24 h p.i. Virus adsorption, determined by assay of residual non-adsorbed virus infectivity and cell-associated, radiolabelled HSV-1, did not differ in the OL cultures. The cumulative data suggest that A/J cells display the same replication pattern as permissive CV-1 cells, whereas the major replicative blocks in the other two murine strains occur at the level of the cytoplasmic membrane in C57BL/6J OLs, and at the level of the nuclear membrane in BALB/cByJ cells.

Adsorption↗

Prolactin and growth hormone levels in different inbred strains of mice: patterns in association with estrous cycle, time of day, and perphenazine stimulation.

These experiments were designed to compare prolactin (PRL) and growth hormone (GH) secretion in strains of mice with varying incidences of mammary tumors. In addition to the basal levels, PRL concentrations were compared after stimulation with perphenazine. Although pituitary concentrations of PRL and pituitary serum concentrations of GH appeared to be generally higher in strains with high incidence of mammary tumors, basal PRL levels in single decapitate serum samples seemed to have little correlation with the incidence of mammary tumors in different strains. However, PRL concentrations in sera after perphenazine injection followed a pattern characteristic of the mammary tumor incidence rate of the strain: C3H/St and CBA/St--the two high-incidence strains--had lower levels of PRL; C57BL/St and BALB/cST--the two low-incidence strains--had higher levels; and DBA/2St--the medium-incidence strain--had an intermediate level. PRL contents of the pituitary glands were depleted virtually equally in all strains except the BALB/cSt. These results suggested that the rate of metabolism of PRL in strains with high incidence of mammary tumors may be faster than in those with low incidences. Perphenazine had no influence on GH secretion in most mice. The strain-specific differences in PRL and GH concentrations were usually present even during cyclical and diurnal fluctuations. Serum PRL and GH levels were generally higher during the follicular phase and lower during the luteal phase of the estrous cycle in both C3H/St and C57BL/St strains. There were signs of episodic secretion of PRL together with evidences of circadian periodicity in the secretion of PRL and GH in mice of both strains. The levels of GH were usually high during the morning hours of those of PRL high during the evening hours. The data show a high degree of specificity in the secretion of PRL and GH im mice of different inbred strains, and it is possible that these strain-specific differences may be an important factor in the development of mammary tumors.

Animals↗

Differential DNA-repair activity in prespermiogenic cells of various mouse strains.

The present report demonstrates differential DNA-repair activity among 14 strains of immature (20 +/- 2 days old) male mice (inbred strains: C57BL/6J, RF/J, Nude homo/nu, RIII/2J, PL/J, AKR/J, Nude hetero/nude, C3H/HeJ, SWR/J, SM/J, ST/J, LP/J, BALB/cJ and random-bred strain: CD-1). The prespermiogenic cells were isolated and enriched by collagenase-trypsin digestion of seminiferous tubules and subsequent 3% albumin-gradient centrifugation. Enriched prespermiogenic cells demonstrated a viability greater than 95% by trypan blue exclusion criteria. For in vitro unscheduled DNA synthesis (UDS) determination, prespermiogenic cells (10(6) cells/ml) were incubated with methyl methanesulfonate (0.4 mM) in the presence of 20 mM hydroxyurea (HU). At 20 mM HU concentration, 90% of S-phase DNA activity in prespermiogenic cells was inhibited and thus, the net UDS activity following MMS exposure was readily determined. MMS-induced UDS activity in the CD-1 mouse strain was both linear up to 4 h of incubation and dose-dependent at 4 h of incubation. The apparent Km for MMS-induced UDS activity in prespermiogenic cells was approx. 1.8 x 10(-4) M. Of the 14 mice strains tested, C57BL/6J and RF/J exhibited the highest DNA-repair activity, while BALB/cJ, LP/J, and ST/J showed the lowest. A maximal difference in UDS activity of 3.5-fold was observed between C57BL/6J and BALB/cJ. Furthermore, a 2.5-fold difference was also noted between RF/J and LP/J mouse strains. Thus, wide variations in DNA-repair activity among 14 mouse strains were clearly demonstrated. Whether genetically select mouse strains with the lowest DNA-repair activity should have greater sensitivity toward environmental mutagens needs to be tested.

Animals↗

Developmental differences of antinociceptive effects of oxotremorine in two inbred strains of mice.

During development the C57BL/6 and DBA/2 mouse strains present morphological variations in cholinergic forebrain structures correlated with different behavioral reactivities to cholinergic agents. The present research assessed that these strain-dependent differences are also present in cholinergic-mediated analgesia. The administration of oxotremorine (0.0025, 0.005 and 0.01 mg/kg) to 30- and 60-day-old C57 and DBA mice resulted in dose- age- and strain-dependent analgesia. In particular oxotremorine is more effective in DBA/2 than in C57BL/6 mice and the latter strain showed a significant decrease of analgesic response in adulthood.

Aging↗

Genetic relationships between sublines of inbred strains of mice as assessed by mandible analysis.

Genetic relationships between sublines of inbred strains of mice were investigated by using mandible measurements. (1) Canonical discriminant analysis (discriminant analysis with reduction of dimensionality) was applied to the investigation of genetic relationships between sublines on two kinds of dimensionality. As a result, it was made clear that all the sublines of the same strains mapped closer to each other than they were to other strains on the plane of z1--z2, except the sublines of strain AA. (2) According to the result of discriminant analysis, misclassification among the sublines of the other strains was only 0 head/302 head, or 0%, for the male mice and 6 head/302 head, or 1.99%, for the female mice. Misidentification between the sublines of the same strain was also of low rate; that is, 28/302, or 9.27%, or the males and 9/302, or 2.98%, for the females. These results suggested that the mice of the sublines of the same strain might be genetically different from one another. (3) The cause for the occurrence of such subline divergence as this seemed to be mainly due to the spontaneous mutation of each colony after the separation of mice. It appeared that the subline divergence of strain AA might be due to the genetic heterozygosity of an original stock before the separation of mice.

Animals↗

Signatures of reproductive isolation in patterns of single nucleotide diversity across inbred strains of mice.

Reproductive isolation is often caused by the disruption of genic interactions that evolve in geographically separate populations. Identifying the genomic regions and genes involved in these interactions, known as "Dobzhansky-Muller incompatibilities," can be challenging but is facilitated by the wealth of genetic markers now available in model systems. In recent years, the complete genome sequence and thousands of single nucleotide polymorphisms (SNPs) from laboratory mice, which are largely genetic hybrids between Mus musculus and M. domesticus, have become available. Here, we use these resources to locate genomic regions that may underlie reproductive isolation between these two species. Using genotypes from 332 SNPs that differ between wild-derived strains of M. musculus and M. domesticus, we identified several physically unlinked SNP pairs that show exceptional gametic disequilibrium across the lab strains. Conspecific alleles were associated in a disproportionate number of these cases, consistent with the action of natural selection against hybrid gene combinations. As predicted by the Dobzhansky-Muller model, this bias was differentially attributable to locus pairs for which one hybrid genotype was missing. We assembled a list of potential Dobzhansky-Muller incompatibilities from locus pairs that showed extreme associations (only three gametic types) among conspecific alleles. Two SNPs in this list map near known hybrid sterility loci on chromosome 17 and the X chromosome, allowing us to nominate partners for disrupted interactions involving these genomic regions for the first time. Together, these results indicate that patterns produced by speciation between M. musculus and M. domesticus are visible in the genomes of lab strains of mice, underscoring the potential of these genetic model organisms for addressing general questions in evolutionary biology.

Animals↗