Inheritance of the serotonin level in 1st-generation mice from crosses with different inbred strains

The level of serotonin content in brain stem and stomach was studied in the first generation of different combinations of inbred mice strains. The serotonin level was shown in these tissues to be inherited differently. Heterosis was observed in the gastro-intestinal tract. Serotonin brain level depends on strain combinations in crosses.     

Genetic analysis of barrel field size in the first somatosensory area (SI) in inbred and recombinant inbred strains of mice

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A?/J, C57BL?/6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15?±?0.10?mm²,?n?=?7) than C57BL?/6J (5.48?±?0.13?mm²,?n?=?10), C3H/HeJ (5.37?±?0.16?mm²,?n?=?10), and A/J mice (5.04?±?0.09?mm²,?n?=?15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n?=?4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses.     

Genetic analysis of barrel field size in the first somatosensory area (SI) in inbred and recombinant inbred strains of mice

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A /J, C57BL /6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15 +/- 0.10 mm(2), n = 7) than C57BL /6J (5.48 +/- 0.13 mm(2), n = 10), C3H/HeJ (5.37 +/- 0.16 mm(2), n = 10), and A/J mice (5.04 +/- 0.09 mm(2), n = 15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n = 4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses.     

Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice.

Interindividual and interstrain variations in cholesterol absorption efficiency occur in humans and animals. We investigated physiological biliary and small intestinal factors that might determine variations in cholesterol absorption efficiency among inbred mouse strains. We found that there were significant differences in cholesterol absorption efficiency measured by plasma, fecal, and lymphatic methods: <25% in AKR/J, C3H/J, and A/J strains; 25-30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and 31-40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In (AKRxC57L)F1 mice, the cholesterol absorption efficiency (31 +/- 6%) mimicked that of the C57L parent (37 +/- 5%) and was significantly higher than in AKR mice (24 +/- 4%). Although biliary bile salt compositions and small intestinal transit times were similar, C57L mice displayed significantly greater bile salt secretion rates and pool sizes than AKR mice. In examining lymphatic cholesterol transport in the setting of a chronic biliary fistula, C57L mice displayed significantly higher cholesterol absorption rates compared with AKR mice. Because biliary and intestinal transit factors were accounted for, we conclude that genetic variations at the enterocyte level determine differences in murine cholesterol absorption efficiency, with high cholesterol absorption likely to be a dominant trait. This study provides baseline information for identifying candidate genes that regulate intestinal cholesterol absorption at the cellular level.     

Exogenous interleukin-2 abrogates differences in the proliferative responses to T cell mitogens among inbred strains of mice.

The proliferative response of spleen cells from BALB/c mice to stimulation with a T cell mitogen, concanavalin A (Con A), was two or more times stronger than that of cells from C57BL/10SnSc (B10) mice. In contrast, the cells from B10 mice responded better to B cell mitogen bacterial lipopolysaccharide (LPS). The differences in the proliferative response to Con A stimulation were not associated with the function of macrophages nor did they depend on IL-1. Spleen cells from BALB/c and B10 mice synthesized comparable amounts of mRNA for IL-1 alpha, and the production of biologically active IL-1 was even higher in the B10 strain. Indomethacin, an inhibitor of prostaglandin synthesis, had no effect on the differences in reactivity between the cells from BALB/c and B10 mice. In addition, no differences in the synthesis of mRNA for the inducible 55-kDa interleukin-2 (IL-2) receptors were found between the spleen cells from BALB/c and B10 mice. However, Con A-stimulated spleen cells from B10 mice produced a significantly lower amount of biologically active IL-2 than similarly stimulated cells from BALB/c mice. In the presence of exogenous IL-2, these low responder spleen cells from the B10 mice responded by proliferation to Con A stimulation to the same extent as cells from the BALB/c mice. These results thus show that a low proliferative response to Con A stimulation in B10 mice was a consequence of a lower production of IL-2 and possibly abrogated the proliferative hyporeactivity produced by exogenous IL-2. We suggest that the differences in the ability to produce IL-2 could be a reason for the discrepancies observed in the immunological responsiveness between BALB/c and B10 mice.     

Rosette formation and humoral immune response to 2,4-dinitrophenol in mice of different inbred strains]

A study was made of the content of rosette-forming cells to DNP-ovalbumin in the spleen of mice of different inbred strains. The values of the rosette-forming cells and of the titre of serum agglutinins to the DNP-group in DNP--bovine gamma-globulin immunization of mice of these strains were determined. It was shown that there were interstrain differences in respect to the normal and immune rosette-forming cells and also humoral antibodies. There was noted a direct correlation between the number of the immune rosette-forming cells and the antibody titre in the serum of mice of the same inbred strain. Immune response (both by the content of rosettes in the spleen and by the antibody level) proved to be the minimal in mice with the highest level of rosette-forming cells. There proved to be no inverse relationship.     

The ultrastructure of the hepatocyte contacts in inbred mice at different ages

Correlation was revealed between the ultrastructure of hepatocyte contacts and force F, essential for the rupture of the junction between the cell, seized with a microneedle, and the tissue specimen, in mice of the highly cancerous CBA line and of the low cancerous C57BL line at the age of 1.7 and 15 months. The most considerable ultrastructural differences in the cell contacts were found in the above mice at the age of 1 month, when the signs of carcinogenic process cannot yet been seen. It is shown that the differences in force F of these mice are not associated with the structural changes in hepatocyte contacts which may be due to the differences in durability properties of the cytoskeleton.     

Importance of biochemical marker genes in inbred strains of mice. Some problems on checking genetic purity of inbred strains (author's transl)

In order to check genetic purity of inbred strains of mice, we surveyed five biochemical variants in certain 69 strains, some of which had established from Japanese fancy mice. The loci examined were Hemoglobin beta-chain, Malic enzyme (supernatant form), Isocitrate dehydrogenase (supernatant form), Serum esterase-1, and Serum esterase-2. These loci were all in homozygous states as far as examined, however some subline divergences were found in a few strains, that is to say, sublines were found to be fixed with different alleles as some loci, Important of biochemical marker genes to check genetic purity of strains and several derived problems are mentioned.     

Sex ratio and litter size in relation to parity and mode of conception in three inbred strains of mice

Breeding records from three inbred strains of mice (BALB/c ABom, C57BL/10ScSn, C3H/He/Kon) were examined with respect to the effects of parity and mode of conception upon litter size and sex ratio at birth. Litters from 3 modes of conception were considered: litters of primipares, litters of multipares conceived during postpartum oestrus and litters conceived after lactational anoestrus. Litters of multipares were assigned to one of these latter groups according to the inter-litter intervals. Parity had no significant effect upon the sex ratio but had a significant one upon the litter size, which did not vary between the strains when first litters were excluded from analysis. The expected variations in response to the mode of conception were found in BALB/c ABom mice but both the effects on the litter size as well as on the sex ratio varied significantly between the strains. Litter size reduction per se could be ruled out to be the cause of the sex ratio variations found. Rather, it is suggested that sex-specificity of embryonic loss depends upon the mode of conception.     

Genotypic differences in the level of N-acetyltransferase activity in mice of inbred lines and their hybrids]

There are "slow" and "rapid" acetylator phenotypes in mice according to N-acetyltransferase activity (E.C. 2.3.1.5) (N-AT). The results of direct, back- and reciprocal crosses of mice lines with rapid acetylation phenotype (C57BL/He) show monogenic autosomic control of acetylation locus (Ac) with rapid allele dominance and sex dependence upon N-AT activity in males. So, genetic polymorphism according to the Ac locus exists in mice as well as in some other animal species and in humans. The results obtained in this study demonstrated the correlation between the N-AT level in mice and their predisposition to malignant tumors as well as dependence of cyclophosphamide action on the N-AT activity upon the genotype of an individual, which suggests a certain role of the Ac locus in tumor development.     

Variations in the behaviors to novel objects among five inbred strains of mice

Novelty stimuli cause various behavioral responses, such as exploration and avoidance, and contextual variables may contribute to the behavioral outputs. Here, we tried to compare the behavioral responses to novel objects of five inbred strains of mice (C57BL/6J, 129/svJae, C3H/HeJ, BALB/cJ and DBA/2J) by using a modified novel object test where a small light-weight cube wrapped with paper was presented to mice in a home cage without beddings. In response to these objects, the C57BL/6J, 129/svJae and C3H/HeJ mice showed mild exploratory behaviors, such as approaching, sniffing or brief contact. In striking contrast, the BALB/cJ and DBA/2J mice, which have been known to show high avoidance/low exploration in other behavioral paradigms, exhibited play-like secondary reactions toward the objects after initial primary exploratory behaviors. Specifically, DBA/2J mice would move the object around in the cage, holding it with their mouths, and BALB/cJ mice would gnaw the object, eventually stripping off the wrapping paper. Such behaviors decreased when similar objects were presented repeatedly. The present results suggest that active manipulations of novel objects may be a relevant parameter for measuring novelty-induced behaviors in mice and appear to be strongly influenced by genetic factors.     

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.     

Genetic and behavioral differences among five inbred mouse strains commonly used in the production of transgenic and knockout mice

Five strains of mice commonly used in transgenic and knockout production were compared with regard to genetic background and behavior. These strains were: C57BL/6J, C57BL/6NTac, 129P3/J (formerly 129/J), 129S6/SvEvTac (formerly 129/SvEvTac) and FVB/NTac. Genotypes for 342 microsatellite markers and performance in three behavioral tests (rotorod, open field activity and habituation, and contextual and cued fear conditioning) were determined. C57BL/6J and C57BL/6NTac were found to be true substrains; there were only 12 microsatellite differences between them. Given the data on the genetic background, one might predict that the two C57BL/6 substrains should be very similar behaviorally. Indeed, there were no significant behavioral differences between C57BL/6J and C57BL/6NTac. Contrary to literature reports on other 129 strains, 129S6/SvEvTac often performed similarly to C57BL/6 strains, except that it was less active. FVB/NTac showed impaired rotorod learning and cued fear conditioning. Therefore, both 129S6/SvEvTac and C57BL/6 are recommended as background strains for targeted mutations when researchers want to evaluate their mice in any of these three behavior tests. However, any transgene on the FVB/NTac background should be transferred to B6. Habituation to the open field was analyzed using the parameters: total distance, center distance, velocity and vertical activity. Contrary to earlier studies, we found that all strains habituated to the open field in at least two of these parameters (center distance and velocity).