The role of genotype, social stress, and season of the year in regulation of hormonal function of murine testis in vitro

Micropopulations consisting of six male mice of different genotypes were studied (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one male). Interlinear differences in the level of social dominance and the effects of genotype, social hierarchy, and season on in vitro testosterone production by testes were examined under different incubation conditions. The testosterone production was estimated under control conditions and under stimulation with human chorionic gonadotropin (CG). Significant genetic differences in the initial and CG-stimulated testosterone production by testes incubated in vitro were found. By the control production, the genotypes fell into two groups: lines C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and DD, high production. By responsiveness of gonads to CG, the genotypes fell into three groups: line CBA/Lac had low testosterone production by testes; lines C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high production. The obtained data indicate stability of genetic polymorphism for the responsiveness of testes to gonadotropins, because neither season nor the formation of social hierarchy could significantly change the interlinear differences. In line PT characterized by high hormonal activity of gonads in the control and under stimulation with gonadotropins, males became dominant in a significantly greater number of cases studied during the formation of hierarchy in micropopulations. The dynamics of both control production of a male sex hormone and responsiveness of testes to CG was established in vitro during the formation of social hierarchy; the effects of season on this dynamics were revealed. Specific characteristics of secretory activity of testes were detected in the control and under stimulation with gonadotropins, depending on incubation conditions. Seasonal and genotypic characteristics of the responsiveness of testes to CG were revealed under different incubation conditions. Genotypic characteristics indicate interlinear differences in the degree of inertia of testosterone biosynthesis on exposure to gonadotropins.     

Role of Genotype, Social Stress, and Season in the Regulation of Hormonal Function of Testes Incubated in Vitro in Mice

Micropopulations consisting of six male mice of different genotypes were studied (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one male). Interlinear differences in the level of social dominance and the effects of genotype, social hierarchy, and season on in vitro testosterone production by testes were examined under different incubation conditions. The testosterone production was estimated under control conditions and under stimulation with human chorionic gonadotropin (CG). Significant genetic differences in the initial and CG-stimulated testosterone production by testes incubated in vitro were found. By the control production, the genotypes fell into two groups: lines C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and DD, high production. By responsiveness of gonads to CG, the genotypes fell into three groups: line CBA/Lac had low testosterone production by testes; lines C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high production. The obtained data indicate stability of genetic polymorphism for the responsiveness of testes to gonadotropins, because neither season nor the formation of social hierarchy could significantly change the interlinear differences. In line PT characterized by high hormonal activity of gonads in the control and under stimulation with gonadotropins, males became dominant in a significantly greater number of cases studied during the formation of hierarchy in micropopulations. The dynamics of both control production of a male sex hormone and responsiveness of testes to CG was established in vitro during the formation of social hierarchy; the effects of season on this dynamics were revealed. Specific characteristics of secretory activity of testes were detected in the control and under stimulation with gonadotropins, depending on incubation conditions. Seasonal and genotypic characteristics of the responsiveness of testes to CG were revealed under different incubation conditions. Genotypic characteristics indicate interlinear differences in the degree of inertia of testosterone biosynthesis on exposure to gonadotropins.     

The Effects of the Genotype and Social Stress on cAMP- and Substrate-Dependent Mechanism Regulating the Hormone-Producing Function of Mouse Testes

Several steps of cAMP- and substrate-dependent testosterone production in the testes were studied with laboratory mouse micropopulations of six inbred strains (A/He, CBA/Lac, C57Bl/6J, DD, YT, PP). The strains differed in basal testosterone production in the gonads and in its response to activation of the adenylate cyclase signal transduction pathway at various steps by human chorionic gonadotropin (hCG), the cholera toxin, forskolin, and dibutyryl-cAMP and in the presence of pregnenolone, an early precursor of testosterone. Establishment of dominant–subordinate relationships in mouse populations substantially affected testosterone production in response to all activators of testicular steroidogenesis. The secretory activity of the testes decreased at the early establishment of social hierarchy in experimental micropopulations, then returned to the initial level, and again decreased in the case of activation with hCG, dibutyryl-cAMP, and pregnenolone. With all activators of steroidogenesis, basal and activated testosterone production changed in the same direction during the establishment and maintenance of social hierarchy, suggesting coordinated changes in all examined steps of testosterone biosynthesis in the testes. The among-strain differences in response to all activators of steroidogenesis remained much the same at various stages of the establishment of social hierarchy. The parameters of cAMP- and substrate-dependent testosterone production averaged over individual stages of the establishment of social hierarchy proved associated. Their genotypic correlations were positive and, in many cases, significant. Subsequent component analysis showed that one principal component accounted for more than 80% of the total among-strain variation, suggesting a coordinated genetic control of the endocrine function of the testes.     

Effect of genotype and social stress on cAMP- and substrate-dependent mechanisms of regulating hormonal function of testis in mice]

Several steps of cAMP- and substrate-dependent testosterone production in the testes were studied with laboratory mouse micropopulations of six inbred strains (A/He, CBA/Lac, C57BL/6J, DD, YT, PT). The strains differed in basal testosterone production in the gonads and in its response to activation of the adenylate cyclase signal transduction pathway at various steps by human chorionic gonadotropin (hCG), the cholera toxin, forskolin, and dibutyryl-cAMP and in the presence of pregnenolone, an early precursor of testosterone. Establishment of dominant-subordinate relationships in mouse populations substantially affected testosterone production in response to all activators of testicular steroidogenesis. The secretory activity of the testes decreased at the early establishment of social hierarchy in experimental micropopulations, then returned to the initial level, and again decreased in the case of activation with hCG, dibutyryl-cAMP, and pregnenolone. With all activators of steroidogenesis, basal and activated testosterone production changed in the same direction during the establishment and maintenance of social hierarchy, suggesting coordinated changes in all examined steps of testosterone biosynthesis in the testes. The among-strain differences in response to all activators of steroidogenesis remained much the same at various stages of the establishment of social hierarchy. The parameters of cAMP- and substrate-dependent testosterone production averaged over individual stages of the establishment of social hierarchy proved associated. Their genotypic correlations were positive and, in many cases, significant. Subsequent component analysis showed that one principal component accounted for more than 80% of the total among-strain variation, suggesting a coordinated genetic control of the endocrine function of the testes.     

Antidepressant-like responses to lithium in genetically diverse mouse strains

A mood stabilizing and antidepressant response to lithium is only found in a subgroup of patients with bipolar disorder and depression. Identifying strains of mice that manifest differential behavioral responses to lithium may assist in the identification of genomic and other biologic factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim test (FST), tail suspension test (TST) and open-field test after acute and chronic systemic and intracerebroventricular (ICV) lithium treatments. Serum and brain lithium levels were measured. Three (129S6/SvEvTac, C3H/HeNHsd and C57BL/6J) of the eight inbred strains tested, and one (CD-1) of the three outbred strains, showed an antidepressant-like response in the FST following acute systemic administration of lithium. The three responsive inbred strains, as well as the DBA/2J strain, displayed antidepressant-like responses to lithium in the FST after chronic administration of lithium. However, in the TST, acute lithium resulted in an antidepressant-like effect only in C3H/HeNHsd mice. Only C57BL/6J and DBA/2J showed an antidepressant-like response to lithium in the TST after chronic administration. ICV lithium administration resulted in a similar response profile in BALB/cJ (non-responsive) and C57BL/6J (responsive) strains. Serum and brain lithium concentrations showed that behavioral results were not because of differential pharmacokinetics of lithium in individual strains, suggesting that genetic factors likely regulate these behavioral responses to lithium. Our results indicate that antidepressant-like responses to lithium in tests of antidepressant efficacy varies among genetically diverse mouse strains. These results will assist in identifying genomic factors associated with lithium responsiveness and the mechanisms of lithium action.     

The Mus musculus domesticus Tdy allele acts later than the Mus musculus musculus Tdy allele: a basis for XY sex-reversal in C57BL/6-YPOS mice.

Consomic C57BL/6 males, carrying either the Mus musculus musculus-derived C57BL/6 Y chromosome or the Mus musculus domesticus-derived Poschiavinus Y chromosome, were outcrossed to females of the inbred strains C3H/Bi and CXBH/By and to females of the random bred strain MF1/Ola. In a study at 12.5 days post coitum, gonads of XYC57 and XYPOS fetuses were assessed for the presence of testicular cords. It was found that XYPOS fetuses had a later onset of testicular development than XYC57 fetuses. Limb development, which was monitored as a measure of overall development, was unaffected by the strain of Y present. These data were supported by a longitudinal study in which the increased growth rate of the testes relative to undifferentiated gonads, was also shown to be delayed in XYPOS fetuses. The extent of the delay was estimated to be approximately 14 h. It is concluded that this delay in the onset of testicular differentiation must be caused by differences between the two Y-chromosome types, most probably allelic differences in the testis determinant Tdy.     

Genetic control of hormone-induced ovulation rate in mice.

The nature of genetic differences in ovarian responsiveness to gonadotropins was examined in mouse strains and subspecies. Hormone-induced ovulation rate (HIOR) differed 5-fold between Mus musculus strains A/J (10.3 +/- 1.6 eggs in cumulus) and C57BL/6J (B6) (47.3 +/- 2.5 eggs in cumulus), and 6-fold among Mus spretus lines and crosses. Subspecies differed up to 10-fold in HIOR (Mus spretus/Ros: 4.8 +/- 1.0 eggs in cumulus versus B6). An additional experiment examined the genetics of HIOR in crosses. The number of eggs ovulated in response to equine chorionic gonadotropin (CG)/human CG averaged 8.4 +/- 0.9 in A/J, 40.7 +/- 1.7 in B6, 33.9 +/- 1.6 in B6AF1, and 20.2 +/- 0.3 in (B6xA)xA backcrosses. The 5-fold genetic differences in hormone-induced ovulation rate between Mus musculus strains A/J and B6 segregated in backcrosses as though they were controlled by the action of approximately 3 loci with major effects. This study demonstrates genetic variation in HIOR both within and between mouse subspecies, and provides confirmation that genetic differences are a major source of variation in the regulation of ovarian responsiveness to gonadotropins.     

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.     

NaCl taste thresholds in 13 inbred mouse strains

Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high-throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests. Using this procedure, we measured NaCl taste thresholds of mice from 13 genealogically divergent inbred stains: 129P3/J, A/J, BALB/cByJ, C3H/HeJ, C57BL/6ByJ, C57BL/6J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/BlNJ, PWK/PhJ, and SJL/J. We found substantial strain variation in NaCl taste thresholds: mice from the A/J and 129P3/J strains had high thresholds (were less sensitive), whereas mice from the BALB/cByJ, C57BL/6J, C57BL/6ByJ, CE/J, DBA/2J, NZB/BINJ, and SJL/J had low thresholds (were more sensitive). NaCl taste thresholds measured in this study did not significantly correlate with NaCl preferences or amiloride sensitivity of chorda tympani nerve responses to NaCl determined in the same strains in other studies. To examine whether strain differences in NaCl taste thresholds could have been affected by variation in learning ability or sensitivity to toxic effects of LiCl, we used the same method to measure citric acid taste thresholds in 4 inbred strains with large differences in NaCl taste thresholds but similar acid sensitivity in preference tests (129P3/J, A/J, C57BL/6J, and DBA/2J). Citric acid taste thresholds were similar in these 4 strains. This suggests that our technique measures taste quality-specific thresholds that are likely to represent differences in peripheral taste responsiveness. The strain differences in NaCl taste sensitivity found in this study provide a basis for genetic analysis of this phenotype.     

Female expression of the H-2-linked sex-limited protein (Slp) due to non-H-2 genes

Female mice of 15 inbred strains in which males express the H-2-linked sex-limited protein (Slp) were tested for the production of this protein. Four inbred strains (FM, LG/J, NZB, PL/J) were found in which females produce Slp in the absence of hormonal manipulation. Crosses have been made between strains FM, NZB, or PL/J and several Slp-negative strains. Slp-typing of the F₁, F₂, and backcross progeny, as well as of a number of recombinant inbred strains, indicates that production of Slp by normal females of these strains depends upon the concurrent presence of an Slp-positive,H-t2-linked allele and of permissive alleles of one or two non-H-2 autosomal genes. Complementation studies with two of the strains (FM and PL) indicate that an identical genetic mechanism mediates expression of Slp in females of these two strains. FM-derived animals carrying the testicular feminization mutation (tfm) also express Slp, as do castrated NZB mice, indicating that Slp expression in these instances is not dependent upon testosterone as it is in other inbred strains. It is concluded from these results that genes distinct from the putative structural gene for Slp influence the sex-limitation of its expression.     

Differential lung mechanics are genetically determined in inbred murine strains.

Genetic determinants of lung structure and function have been demonstrated by differential phenotypes among inbred mice strains. For example, previous studies have reported phenotypic variation in baseline ventilatory measurements of standard inbred murine strains as well as segregant and nonsegregant offspring of C3H/HeJ (C3) and C57BL/6J (B6) progenitors. One purpose of the present study is to test the hypothesis that a genetic basis for differential baseline breathing pattern is due to variation in lung mechanical properties. Quasi-static pressure-volume curves were performed on standard and recombinant inbred strains to explore the interactive role of lung mechanics in determination of functional baseline ventilatory outcomes. At airway pressures between 0 and 30 cmH2O, lung volumes are significantly (P < 0.01) greater in C3 mice relative to the B6 and A/J strains. In addition, the B6C3F1/J offspring demonstrate lung mechanical properties significantly (P < 0.01) different from the C3 progenitor but not distinguishable from the B6 progenitor. With the use of recombinant inbred strains derived from C3 and B6 progenitors, cosegregation analysis between inspiratory timing and measurements of lung volume and compliance indicate that strain differences in baseline breathing pattern and pressure-volume relationships are not genetically associated. Although strain differences in lung volume and compliance between C3 and B6 mice are inheritable, this study supports a dissociation between differential inspiratory time at baseline, a trait linked to a putative genomic region on mouse chromosome 3, and differential lung mechanics among C3 and B6 progenitors and their progeny.     

Genes regulating testis size.

The studies described here provide information about the genetic and morphological bases for the significant differences in testis size among three closely related C57BL mouse substrains: C57BL/6J, C57BL/6ByJ, and C57BL/10J. C57BL/6J mice have normal-size testes while the other two substrains have small-size testes. Genes controlling testis size are postulated to be among the estimated forty genes that differ between the C57BL/6J and C57BL/6ByJ substrains. The number of genes involved in testis size regulation was examined using recombinant inbred mouse strains. An investigation of the role of Y chromosome genes was performed by completing molecular analyses with a mouse Y chromosome-specific probe. Sertoli and germ cell counts provided insight into the morphological basis for the different testis sizes. The experimental results suggest that there are at least two autosomal testis-size genes and that they control testis size by regulating the number of Sertoli cells.     

Effect of genotype on hormonal function formation of Leydig cells during mouse postnatal development

Changes in in vitro testosterone production by Leydig cells induced by chorionic gonadotropin, dibutyryl-cAMP, and pregnenolone have been studied during postnatal development of four inbred mouse strains BALB/c, PT, CBA/Lac, and A/He, with contrast hormonal activity of testes in sexually mature males. The interlinear differences significantly change with age of the males by all studied indices indicating genotype-dependent formation of hormonal activity of Leydig cells during postnatal development. Coordinated interlinear variability between all indices of Leydig cells reactivity has been established for each studied period of postnatal development. Hence, we have established coordinated interlinear genetic variability of hormonal function of Leydig cells, which was confirmed by considerable changes in it during postnatal development at puberty. Definitive genotypic differences in hormonal activity of Leydig cells appeared by late pubertal and early postpubertal development (day 60) and coincided with termination of morphological differentiation of Leydig cells and appearance of the differentiated cell population.     

Effect of Genotype on Formation of Hormonal Function of Leydig Cells during Mouse Postnatal Development

Changes in in vitro testosterone production by Leydig cells induced by chorionic gonadotropin, dibutyryl-cAMP, and pregnenolone have been studied during postnatal development of four inbred mouse strains BALB/c, PT, CBA/Lac, and A/He, with contrast hormonal activity of testes in sexually mature males. The interlinear differences significantly change with age of the males by all studied indices indicating genotype-dependent formation of hormonal activity of Leydig cells during postnatal development. Coordinated interlinear variability between all indices of Leydig cells reactivity has been established for each studied period of postnatal development. Hence, we have established coordinated interlinear genetic variability of hormonal function of Leydig cells, which was confirmed by considerable changes in it during postnatal development at puberty. Definitive genotypic differences in hormonal activity of Leydig cells appeared by late pubertal and early postpubertal development (day 60) and coincided with termination of morphological differentiation of Leydig cells and appearance of the differentiated cell population.     

High-throughput phenotypic assessment of cardiac physiology in four commonly used inbred mouse strains

Mice with genetic alterations are used in heart research as model systems of human diseases. In the last decade there was a marked increase in the recognition of genetic diversity within inbred mouse strains. Increasing numbers of inbred mouse strains and substrains and analytical variation of cardiac phenotyping methods require reproducible, high-throughput methods to standardize murine cardiovascular physiology. We describe methods for non-invasive, reliable, easy and fast to perform echocardiography and electrocardiography on awake mice. This method can be used for primary screening of the murine cardiovascular system in large-scale analysis. We provide insights into the physiological divergence of C57BL/6N, C57BL/6J, C3HeB/FeJ and 129P2/OlaHsd mouse hearts and define the expected normal values. Our report highlights that compared to the other three strains tested C57BL/6N hearts reveal features of heart failure such as hypertrophy and reduced contractile function. We found several features of the mouse ECG to be under genetic control and obtained several strain-specific differences in cardiac structure and function.     

Genetic variation in androgen regulation of ornithine decarboxylase gene expression in inbred strains of mice

Previous studies have indicated that androgen regulation of certain gene products in murine kidney is genetically controlled. In the present work, the expression of renal ornithine decarboxylase (ODC) gene(s) was used as a biological marker to study androgen responsiveness of eight inbred strains of mice (A/J, C57BR/cdJ, 129/J, C57L/J, BALB/cJ, SM/J, RF/J, and C57BL/6J). Kidneys of untreated females from these strains did not have significantly different basal ODC activities or ODC mRNA concentrations. However, renal enzyme concentrations in intact male mice exhibited marked strain-dependent variation; three strains (RF/J, SM/J, and C57BR/cdJ) had 5- to 20-fold higher activities than the other five strains. Renal ODC mRNA content showed similar genetic variability in the male mice; animals with highest enzyme activity had higher mRNA levels than those with low activity. These results could not be explained by differences in either serum testosterone levels or renal nuclear androgen receptor content, suggesting that the animals were differentially sensitive to endogenous androgens. To evaluate further the androgen regulation of ODC gene expression, female mice were treated with testosterone-releasing implants for 5-7 days. The two strains (A/J and C57BL/6J) that had low enzyme activity in response to endogenous testosterone in male mice also showed blunted responses to exogenous androgen administration, as measured by the induction of ODC and its mRNA. The relative distribution of the two mRNA species coding for ODC (2.2 and 2.7 kb in size) exhibited strain-dependent variation that did not, however, correlate with the androgen responsiveness. Studies of the mRNA levels in reciprocal F1 hybrids of C57BR/cdJ and C57BL/6J mice suggested that androgen sensitivity of ODC gene expression, at least in these crosses, was inherited in an autosomal dominant manner.     

A search for strain differences in response of mice to mutagenesis by thio-TEPA

After treatment of mice with thio-TEPA Malashenko and colleagues found differences among inbred strains in yield of dominant lethals and of chromosome aberrations in bone marrow, which they attributed to genes affecting repair. An attempt was made to confirm this work by comparing yields of dominant lethals in different strains of females mated to the same strain of males. However, no differences were found, all strain combinations giving 42-49% dominant lethals after a dose of 2 mg/kg thio-TEPA to late spermatids. Thus, the existence of genetic differences in repair of thio-TEPA induced lesions between strains CBA and C57BL/6J and between C3H/He and 101/H is not confirmed. Possible reasons for the discrepant results are discussed.     

Normal Testis Determination in the Mouse Depends on Genetic Interaction of a Locus on Chromosome 17 and the Y Chromosome

We previously described a locus on chromosome (Chr) 17 of the mouse that is critical for normal testis development. This locus was designated "T-associated sex reversal" (Tas) because it segregated with the dominant brachyury allele hairpin tail (Thp) and caused gonads of C57BL/6J XY, Thp/+ individuals to develop as ovaries or ovotestes rather than as testes. To clarify the inheritance of Tas, we investigated the effects of T-Orleans (TOrl), another brachyury mutation, on gonad development. We found that gonads of C57BL/6J XY, Thp/+ and TOrl/+ mice develop ovarian tissue if the Y chromosome is derived from the AKR/J inbred strain, whereas normal testicular development occurs in the presence of a Y chromosome derived from the C57BL/6J inbred strain. From these observations we conclude that: (1) Tas is located in a region on Chr 17 common to the deletions associated with Thp, and TOrl, and (2) the Y-linked testis determining gene, Tdy, carried by the AKR/J inbred strain differs from that of the C57BL/6J inbred strain. We suggest that in mammals Tdy is not the sole testis determinant because autosomal loci must be genetically compatible with Tdy for normal testicular development.     

Behavioral, physiological, and molecular differences in response to dietary restriction in three inbred mouse strains

Food restriction paradigms are widely used in animal studies to investigate systems involved in energy regulation. We have observed behavioral, physiological, and molecular differences in response to food restriction in three inbred mouse strains, C57BL/6J, A/J, and DBA/2J. These are the progenitors of chromosome substitution and recombinant inbred mouse strains used for mapping complex traits. DBA/2J and A/J mice increased their locomotor activity during food restriction, and both displayed a decrease in body temperature, but the decrease was significantly larger in DBA/2J compared with A/J mice. C57BL/6J mice did not increase their locomotor activity and displayed a large decrease in their body temperature. The large decline in body temperature during food restriction in DBA/2J and C57BL/6J strains was associated with a robust reduction in plasma leptin levels. DBA/2J mice showed a marked decrease in white and brown adipose tissue masses and an upregulation of the antithermogenic hypothalamic neuropeptide Y Y(1) receptor. In contrast, A/J mice showed a reduction in body temperature to a lesser extent that may be explained by downregulation of the thermogenic melanocortin 3 receptor and by behavioral thermoregulation as a consequence of their increased locomotor activity. These data indicate that genetic background is an important parameter in controlling an animal's adaptation strategy in response to food restriction. Therefore, mouse genetic mapping populations based on these progenitor lines are highly valuable for investigating mechanisms underlying strain-dependent differences in behavioral physiology that are seen during reduced food availability.     

Genetic polymorphisms among C57BL/6 mouse inbred strains

Mice from the inbred C57BL/6 strain have been commonly used for the generation and analysis of transgenic and knockout animal models. However, several C57BL/6 substrains exist, and these are genetically and phenotypically different. In addition, each of these substrains can be purchased from different animal providers and, in some cases, they have maintained their breeding stocks separated for a long time, allowing genetic differences to accumulate due to individual variability and genetic drift. With the aim of describing the differences in the genotype of several C57BL/6 substrains, we applied the Illumina^® Mouse Medium Density Linkage Mapping panel, with 1,449 single nucleotide polymorphisms (SNPs), to individuals from ten C57BL/6-related strains: C57BL/6JArc, C57BL/6J from The Jackson Lab, C57BL/6J from Crl, C57BL6/JRccHsd, C57BL/6JOlaHsd, C57BL/6JBomTac, B6(Cg)-Tyr ^c?2j /J, C57BL/6NCrl, C57BL/6NHsd and C57BL/6NTac. Twelve SNPs were found informative to discriminate among the mouse strains considered. Mice derived from the original C57BL/6J: C57BL/6JArc, C57BL/6J from The Jackson Lab and C57BL/6J from Crl, were indistinguishable. Similarly, all C57BL/6N substrains displayed the same genotype, whereas the additional substrains showed intermediate cases with substrain-specific polymorphisms. These results will be instrumental for the correct genetic monitoring and appropriate mouse colony handling of different transgenic and knockout mice produced in distinct C57BL/6 inbred substrains.