Muscarinic receptors in brain from four strains of inbred mice

The density of brain muscarinic receptors from four strains of inbred mice was determined. C57BL/6J mice had a significantly higher density of muscarinic receptors in the forebrain than Balb/cJ or C57BL/10J mice. In the midbrain, C57BL/6J mice also had the highest density of receptors and in the hindbrain, C57BL/6J and AKR/J mice had a two fold higher receptor density compared to the other two strains. These findings demonstrate that inbred strains of mice which exhibit a range of genetically-determined behaviors, have varying densities of muscarinic receptors.     

The ear-leaf percentage of calcium and magnesium in maize inbred lines and their diallel progeny

Summary Eight maize (Zea mays L.) inbred lines and their single cross hybrids were grown for one year under field conditions near Osijek. The ear-leaf was taken in the tasseling stage and analysed for Ca and Mg percentage. Parental effects on ear-leaf content of Ca and Mg were very high. The hybrids of line C103 had low mean percentages of ear-leaf Ca and Mg while the hybrids of line Os64 had high mean percentages.     

Gangliosides in various brain areas of three inbred strains of mice

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, termed here GT1L, was located between GD1b and GT1b. This ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p<0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri-and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.     

Gene mapping of sperm quality parameters in recombinant inbred strains of mice

The aim of this study was to map chromosomal regions containing hypothetical genes responsible for the following parameters of mouse semen quality: (1) the percentage of sperm with abnormal head morphology, (2) the level of dead spermatozoa, (3) the percentage of sperm tails with residual cytoplasmic droplets, and (4) the percentage of sperm with impaired sperm tail membrane integrity. We also analyzed any possible correlations between these parameters. The most appropriate animal model for mapping genes controlling quantitative traits (QTL, quantitative trait locus) is a set of recombinant inbred (RI) strains. The set of RI strains used in this study was derived from crosses between two inbred mouse strains, KE and CBA/Kw, which differ significantly in fertility parameters and gamete quality. We analyzed the four parameters of sperm quality in male mice from two parental strains and from 12 RI strains. The strain distribution pattern (SDP) of 187 polymorphic microsatellite markers was prepared for 20 chromosomes of the mouse genome in 12 RI strains. We correlated the SDP of these markers with the values of sperm quality parameters, using MapManager QTX software (ver. b18). The mapping procedure indicated that the percentage of sperm with abnormal head morphology is controlled by gene(s) located in chromosomal regions 11q24, 11q31 and 6q15.6. There was also a strong correlation between male body weight and the hypothetical gene(s) in chromosomal region 18q47. A detailed analysis of the genes located in these regions enabled us to prepare a list of candidate genes. We discuss the basis of the correlation between the measured parameters.     

Cyclic nucleotide levels in the brain of inbred mice in emotional stress exposure

The content of cAMP and cGMP in different brain regions was studied in C57Bl/6 and BALB/c mice at rest and upon exposure to emotional stress induced by open field technique. Interstrain differences in baseline nucleotide content, differences in nucleotide distribution in the brain regions and changes in their concentration after stress have been revealed.     

Analysis of the specific 3H-diazepam binding in the brain of inbred mice with differing emotionality

The influence of sodium chloride and gamma-aminobutyric acid (GABA) on H3-diazepam binding in CNS membrane fraction were investigated in C57Bl/6, BALB/c mice and their F1 hybrids. The addition of GABA (1, 10 and 100 microM) elevated the level of radioligand binding with CNS membranes in all the inbred mice in similar manner. The higher stimulating effect of sodium chloride (50, 100 and 150 mM) on the H3-diazepam reception was found in BALB/c mice and F1 hybrids, as compared to C57Bl/6 mice. It has been suggested that membrane-dependent conformational reconstructions of supramolecular receptor complex are the cause of genetic differences in the regulation of H3-diazepam reception by Cl(-)-ionophore.     

The polyphyletic origin of laboratory inbred mice and their rate of evolution

The analysis of various genetic components in the standard inbred laboratory strains of mice shows that several taxonomic units of the complex species Mus musculus have contributed to their genetic background. These laboratory lines are often taken as archetypes of the mammalian genome and since their genealogy is known for around 80 years they have been used to estimate mutation rates and various other evolutionary parameters. The knowledge of their origins is important if one is to avoid erroneous interpretations. Do they possess haplotypes that could have existed in natural populations of M. musculus domesticus or are they the fruit of artificial recombinations between divergent genomes? We discuss this in the light of various genetic systems.     

Effect of brain acid extract products in inbred mice on 3H-diazepam reception

The influence of brain acid extract products, isolated by high-performance liquid chromatography on H3-diazepam binding was investigated in synaptosomal membranes of C57BL/6 and BALB/c mice. Fractions with stimulatory and inhibitory activity were isolated. Quantitative and qualitative differences in the effects and structure of ACTH-immunoreactive peptide fractions under study were established.     

Analysis of the spectrum of ACTH-immunoreactive peptides in the brain of inbred mice

The ACTH-immunoreactive peptides (IP) distribution in the acid extract of brain and plasma fractions of C57BL/6, BALB/c and F1 (C57BL/6 X BALB/c) mice was investigated. IP were isolated by high-performance liquid chromatography. Interstrain differences in the IP spectrum were found in intact mice and mice after exposure to stress in the "open-field" test.     

Responses to novelty in two inbred strains of mice and their F1 hybrids: Behaviour and brain biogenic amines

Responses to novelty of two inbred strains of mice, C57BL/6JOrl (C) and A/JOrl (A) and their reciprocal F₁ hybrids were recorded. The parental strains differed from each other: the C strain showed a preference for a novel environment and neophobic reactions to a novel object introduced into the familiar environment. The A mice were characterized by a preference for the familiar environment and lower neophobia towards the novel object. In addition, the C strain exhibited high and the A strain low locomotor activity. The reciprocal hybrids were identical in their major responses to the C strain. Neurochemical investigations indicated that the parental A strain showed a lower level of dopamine in the striatum and in the olfactory bulbs when compared with the C strain and the hybrid F₁ C × A.     

Free amino acid pool in the brain of inbred strains of mice with different learning aptitudes]

GABA, glycine, taurine, putative inhibitory transmitters or modulators of the CNS are at a significantly lower level in the brains of SEC and DBA strains of mice which offer higher performances in avoidance and learning tests than in the C57 strain which scores poorly.     

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.     

Evaluation of heritable determinants of blood and brain serotonin homeostasis using recombinant inbred mice

The biogenic amine serotonin (5‐HT, 5‐hydroxytryptamine) exerts powerful, modulatory control over multiple physiological functions in the brain and periphery, ranging from mood and appetite to vasoconstriction and gastrointestinal motility. In order to gain insight into shared and distinct molecular and phenotypic networks linked to variations in 5‐HT homeostasis, we capitalized on the stable genetic variation present in recombinant inbred mouse strains. This family of strains, all derived from crosses between C57BL/6J and DBA/2J (BXD) parents, represents a unique, community resource with approximately 40 years of assembled phenotype data that can be exploited to explore and test causal relationships in silico. We determined levels of 5‐HT and 5‐hydroxyindoleacetic acid from whole blood, midbrain and thalamus/hypothalamus (diencephalon) of 38 BXD lines and both sexes. All 5‐HT measures proved highly heritable in each region, although both gender and region significantly impacted between‐strain correlations. Our studies identified both expected and novel biochemical, anatomical and behavioral phenotypes linked to 5‐HT traits, as well as distinct quantitative trait loci. Analyses of these loci nominate a group of genes likely to contribute to gender‐ and region‐specific capacities for 5‐HT signaling. Analysis of midbrain mRNA variations across strains revealed overlapping gene expression networks linked to 5‐HT synthesis and metabolism. Altogether, our studies provide a rich profile of genomic, molecular and phenotypic networks that can be queried for novel relationships contributing risk for disorders linked to perturbed 5‐HT signaling .     

Susceptibility of inbred mice to Leishmania tropica infection: correlation of susceptibility with in vitro defective macrophage microbicidal activities

Eleven mouse strains were inoculated in footpads with amastigotes of Leishmania tropica and observed for 12 weeks. Liver and spleen impression smears from infected mice were examined for the presence of intracellular parasites. Four strains (BALB/cJ, C57L/J, NZW/N, and P/J) failed to heal the subcutaneous lesion and showed evidence of systemic infection; the remaining seven strains (A/J, C3H/HeJ, C3H/HeN, C3HeB/FeJ, C57BL/6J, C57BL/10J, and C57BL/10ScN) were each resistant to infection and resolved their lesions by Week 10. Macrophages from the four susceptible strains could not be activated to kill L. tropica amastigotes by treatment with soluble lymphocyte products in vitro. In contrast, macrophages from all seven resistant strains responded to lymphokine treatment and eliminated 80-90% of intracellular parasites. These results suggest that in vitro macrophage microbicidal activities predict the course of systemic leishmanial disease.