Behavioral Differences Between C57BL/6J × FVB/NJ and C57BL/6J × NZB/B1NJ F1 Hybrid Mice: Relation to Control of Ethanol Intake

C57BL/6J × FVB/NJ F1 (B6 × FVB) mice consume more alcohol than C57BL/6J × NZB/B1NJ F1 (B6 × NZB) mice and this high alcohol consumption is stable after abstinence whereas B6 × NZB show reduced consumption, thus providing models of Sustained Alcohol Preference (SAP) and Reduced Alcohol Preference (RAP). In female hybrids, we assessed several behavioral responses to define behaviors which might predict SAP and RAP. B6 × FVB exhibited less severe ethanol-induced conditioned taste aversion and were less sensitive to ethanol-induced loss of righting reflex than B6 × NZB. Both hybrids demonstrated ethanol-induced place preference and a low ethanol withdrawal severity. We found that these hybrids differ in their sensitivity to the aversive and sedative, but not rewarding, effects of ethanol. Results of elevated plus maze, mirror chamber, and locomotor tests reveal B6 × FVB mice are less anxious and more active than B6 × NZB mice. Results obtained offer insights about factors that determine SAP and RAP in these new genetic models of alcohol consumption.     

Food intake,water intake,and drinking spout side preference of 28 mouse strains

Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/HlJ, LP/J, NOD/LtJ, NZB/BlNJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were fed chow and had access to two water bottles. Body weight, food intake, water intake, and drinking spout side preference were measured. There were large strain differences in all the measures collected, with at least a two-fold difference between strains with the lowest and the highest trait values. Estimates of heritability ranged from 0.36 (spout side preference) to 0.87 (body weight). Body weight, food intake, and water intake were interrelated among the strains, although substantial strain variation in food and water intakes independent from body weight was present. The strain differences described here provide useful information for designing mutagenesis screens and choosing strains for genetic mapping studies.     

Voluntary consumption of NaCl,KCl, CaCl2, and NH4Cl solutions by 28 mouse strains

Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/H1J, LP/J, NOD/LtJ, NZB/B1NJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were tested with NaCl (75–450 mM), KCl (30–300 mM), CaCl₂ (3–100 mM), and NH4Cl (10–300 mM) solutions using two-bottle preference tests with water as the second choice. For each mineral, there was a wide range of strain variation in solution intakes and preferences. This variation had a substantial genetic component as assessed using heritability estimates. In most cases, the strain means were continuously distributed; however, strains with deviating high or low intakes or preferences were also observed. The associations among the responses to different minerals were only modest, suggesting distinct genetic controls of sodium, potassium, calcium, and ammonium consumption. These results provide a valuable resource for investigators who wish to identify genes involved in the regulation of mineral consumption and balance.     

Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross

Consumption of ethanol solutions by rodents in two-bottle choice tests is a model to study human alcohol intake. Mice of the C57BL/6ByJ strain have higher ethanol preferences and intakes than do mice of the 129P3/J strain. F2 hybrids between these two strains were phenotyped using two-bottle tests involving a choice between water and either 3% or 10% ethanol. High ethanol preferences and intakes of the B6 mice were inherited as additive or dominant traits in the F2 generation. A genome screen using these F2 mice identified three significant linkages. Two loci, on distal chromosome 4 (Ap3q) and proximal chromosome 7 (Ap7q), strongly affected 10% ethanol intake and weakly affected 3% ethanol intake. A male-specific locus on proximal chromosome 8 (Ap8q) affected 3% ethanol preference, but not indexes of 10% ethanol consumption. In addition, six suggestive linkages (on chromosomes 2, 9, 12, 13, 17, and 18) affecting indexes of 3% and/or 10% ethanol consumption were detected. The loci with significant and suggestive linkages accounted for 35-44% of the genetic variation in ethanol consumption phenotypes. No additive-by-additive epistatic interactions were detected for the primary loci with significant and suggestive linkages. However, there were a few modifiers of the primary linkages and a number of interactions among unlinked loci. This demonstrates a significant role of the genetic background in the variation of ethanol consumption.     

Tolerance induction as an index of age-related changes.

Tolerance to rabbit gamma globulin RGG) can be induced in newborn or three week old mice of all strains tested. In six week old SJL or NZB mice there is marked resistance against tolerance induction to RGG. This resistance increases with increasing age and is completed by the age of 12 weeks. Resistance to tolerance can be observed in 3 week old SJL animals when human IgG3 but not when human IgG1 or RGG is employed as tolerogen. Using IgG3, resistance to tolerance induction can be demonstrated in 28-34 week old A/J, C57BL/6J and DBA1/J mice. Thus resistance to tolerance induction seems to be a concomitant of aging; SJL and NZB differ from other strains only by the age at which this change is apparent. By the 6th week of age, SJL and NZB mice develop marked resistance to tolerance induction with RGG, and so do hybrids between these two strains; there is no complementation with respect to resistance against tolerance induction. Aggregate-freed iodinated rabbit gamma globulin (125I-RGG) but not mouse immunoglobulin is eliminated much more rapidly from the body of normal 6 week old SJL and NZB mice than from the body of hybrids. Complementation in the hybrids might occur and prevent a response to small quantities of aggregate-freed RGG.     

Tolerance Induction as an Index of Age-Related Changes (1)

Tolerance to rabbit gamma globulin (RGG) can be induced in newborn or three week old mice of all strains tested. In six week old SJL or NZB mice there is marked resistance against tolerance induction to RGG. This resistance increases with increasing age and is completed by the age of 12 weeks. Resistance to tolerance can be observed in 3 week old SJL animals when human IgG3 but not when human IgG1 or RGG is employed as tolerogen. Using IgG3, resistance to tolerance induction can be demonstrated in 28-34 week old A/J, C57BL/6J and DBA1/J mice. Thus resistance to tolerance induction seems to be a concomitant of aging; SJL and NZB differ from other strains only by the age at which this change is apparent. By the 6th week of age, SJL and NZB mice develop marked resistance to tolerance induction with RGG, and so do hybrids between these two strains; there is no complementation with respect to resistance against tolerance induction. Aggregate-freed iodinated rabbit gamma globulin (¹²⁵I-RGG) but not mouse immunoglobulin is eliminated much more rapidly from the body of normal 6 week old SJL and NZB mice than from the body of hybrids. Complementation in the hybrids might occur and prevent a response to small quantities of aggregate-freed RGG.     

Genetic variation in the development of mouse brain and behavior: evidence from the middle postnatal period.

Six inbred strains and 3 F2 hybrid crosses of mice were assessed for developmental status at 32 days after conception (about 13 days after birth). Phenotypes measured included body weight, brain weight, maturity of 14 reflexive behaviors, myelination of 80 fiber tracts, and thickness of the external granular layer of the cerebellum. All measures of brain and behavior showed a similar pattern of results: hybrids were generally more advanced than either of their inbred parent strains; differences among inbred strains were large, but differences among hybrid crosses were quite small. Acceleration of F2 mice compared to their homozygous relatives ranged from .5 to 2.4 days mean difference. Developmental ages of inbred litters ranged from 28.7 to 32.2 days, whereas hybrid litters ranged from 31.5 to 32.7 days.     

Spontaneous antiidiotypic antibodies to the NZB Coombs autoantibody.

We have further investigated the phenomenon of spontaneous anti-(Coombs) antiidiotypic antibodies in the F1 hybrids of New Zealand black (NZB) and CBA mice. These mice show an age-related increase in incidence of such antiidiotype during the first year of life. There is no difference between males and females in the occurrence of antiidiotype. Reciprocal hybrids are both affected, so that maternal influence from the NZB strain is not critical. The antiidiotype also occurs in spite of the xid gene. We have so far detected such spontaneous antiidiotype only in (CBA X NZB)F1 hybrids and not in hybrids of NZB with two other strains or in a variety of recombinant inbred strains between NZB and C58. Our results to data suggest extensive shared idiotypy among NZB mice and a limited number of total idiotypes.     

Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice.

When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results.     

Genetic Control of Resistance to Mercury-Induced Immune/Autoimmune Activation

Previous studies have shown that genetic factors control the susceptibility to mercury-induced immunoglobulin (Ig)G1 antibody formation, IgE synthesis, renal IgG deposits and antinucleolar autoantibodies (ANolA) production in the susceptible mice. In this study, we examined the genetic control of resistance to these characteristics after HgCl2 injection in F1 hybrid crosses between the highly mercury resistant DBA/2 and mercury susceptible NZB (H-2d), SJL (H-2 s), A.CA (H-2f) and DBA/1 (H-2q) mice and also in backcross hybrids between (DBA/2 x SJL)F1 and SJL mice. We observed that mercury-induced immune/autoimmune manifestations were profoundly downregulated in most (if not all) of the F1 hybrids, indicating that the resistance to mercury was a dominant trait. Analysis of mercury-induced immune/autoimmune responses in the (DBA/2 x SJL) x SJL backcross hybrids suggested that only one gene or a cluster of genes determined the resistance to the ANolA production, whereas the resistance to other characteristics was controlled by two and/or three gene loci. By H-2 genotyping the backcross mice, it was found that H-2d haplotype per se could confer resistance to ANolA production. However, we did not find any significant association between the H-2d haplotype and the resistance to increase of IgG1 and IgE synthesis and the development of renal IgG1 deposits. Thus, while in DBA/2 mice, gene(s) in the H-2 loci strictly contribute to the inheritance of resistance to ANolA production; non-H-2 genes mainly govern the inheritance of unresponsiveness regarding other characteristics.     

Effect of the BXSB Y chromosome accelerating gene on autoantibody production

The Y chromosome of the BXSB mouse is able to accelerate and adversely alter the autoimmune disease of inbred BXSB mice and in male F1 hybrids. In order to further study the effects of the BXSB Y chromosome, we developed three inbred congenic strains, each bearing the BXSB Y: CBA/J.BXSB-Y, NZW.BXSB-Y, and NZB.BXSB-Y. The BXSB Y did not induce anti-DNA or anti-red blood cell (RBC) autoantibodies in either CBA/J or NZW congenic strains. Thus, it is an accelerating rather than an inducing factor. NZB.BXSB-Y congenic mice had accelerated anti-RBC but not anti-DNA. Studies of recombinant inbred by BXSB F1 mice indicated that the BXSB Y did not act to promote the activity of the NZB gene underlying anti-DNA. These and studies of (BXSB X NZB.BXSB-Y) F1 mice suggested that BXSB autosomal genes are required for the full anti-DNA accelerating activity of the BXSB Y. These mice provide a basis for future molecular genetic studies of the BXSB Y.     

Genetic regulation of hypergammaglobulinaemia and the correlation to autoimmune traits in (NZB X NZW) F1 hybrid

To determine the inheritance patterns of both IgM class and IgG class hypergammaglobulinaemias, the locations of genes and the relations of these genes to other autoimmune traits in NZB X NZW (B/W) F1 hybrid, we measured serum levels of both IgM and IgG in NZB, NZW, B/W F1 hybrid, B/W F1 X NZW back-cross and B/W F1 X NZB back-cross mice. The highest serum IgM levels were observed in NZB mice, however the serum IgG levels were normal. In contrast, a large amount of IgG was produced in B/W F1 hybrids, in which the serum IgM levels were lower than those observed in NZB mice. The NZW mice had fairly normal values for both measures. Progeny studies suggested that a single dominant locus (Imh-1) of NZB strain, which is loosely linked to brown-black coat colour locus b and Mup-1 locus on chromosome 4, determines the IgM class hypergammaglobulinaemia. The estimated gene order was Mup-1:b:Imh-1. This IgM class hypergammaglobulinaemia in NZB mice was suppressed to a considerable extent in B/W F1 hybrid mice by either a gene dosage effect or more likely, a regulatory gene locus of NZW strain, being also loosely linked to Mup-1 locus on chromosome 4. As for the IgG class hypergammaglobulinaemia, a complementary effect of two or three genes, either one or two dominant genes derived from NZB and a single dominant gene from NZW strains, determines this trait in B/W F1 hybrid mice. There appeared to be no relationships between the genes responsible for the IgM class and IgG class hypergammaglobulinaemias. When looking at the correlations between the hypergammaglobulinaemias and the traits, anti-double stranded DNA (dsDNA) antibodies and renal disease in both back-cross mice, we found a significant quantitative correlation only between the IgG class hypergammaglobulinaemia and the IgG class anti-dsDNA antibodies in B/W F1 X NZB back-cross mice.     

Short-Term Selective Breeding as a Tool for QTL Mapping: Ethanol Preference Drinking in Mice

Short-term selective breeding starting from an F₂ intercross of two inbred strains is a largely unexploited but potentially useful tool for quantitative trait locus (QTL) mapping. The selection lines can also serve as a valuable confirmation test of recornbinant inbred (RI) QTL results when the same two progenitor strains are used. Starting from an F₂ from a C57BL/6J (B6) × DBA/2J (D2) cross (B6D2F2), this approach was used in a population of ~72 mice per generation bidirectionally selected for two-bottle choice 10% ethanol (alcohol) preference for four generations. The high-preference line diverged significantly from the low line in the first generation with a realized heritabittty of .32. By generation 4, the preference ratios in the high line were double those seen in the low line. Regions of the genome previously implicated by BXD RI QTL analysis as containing QTLs were searched using microsatellite markers. The test for the presence of QTLs was based on the divergence of marker allele frequencies in the two oppositely selected lines significantly exceeding that expected from random (genetic) drift and allele frequency estimation error. Combining the BXD and two-way selection line results, the most probable QTL was found on chromosome 3 (near the AdhI locus; LOD ~2.9), other probable QTLs were found with LOD 2.4–2.6.     

Accelerated autoimmune disease and lymphoreticular neoplasms in F1 hybrid PN/NZB and NZB/PN mice

This report describes the first studies of inheritance of autoimmunity in inbred Palmerston North (PN) mice, a model of systemic lupus erythematosus (SLE). Mating of PN mice with the nonautoimmune DBA/2 strain produced evidence that PN disease had a recessive mode of inheritance. When PN mice were crossed with autoimmune NZB mice, female offspring from both crosses developed anti-DNA antibodies and died prematurely with vasculitis, renal disease, and lymphomas. In contrast, reciprocal hybrid males had different patterns of mortality; PN/NZB males from the PN female X NZB male mating had moderately prolonged life spans, whereas NZB/PN males from the opposite cross (NZB female X PN male) had prolonged survival to the mean age of 104 weeks. To determine if testicular hormones were solely responsible for increased longevity in hybrid males, PN/NZB and NZB/PN mice were castrated at 2 weeks of age and compared to sham-operated littermate controls. Prepubertal castration did not influence longevity in PN/NZB males, but loss of gonadal hormones significantly reduced life spans in reciprocal NZB/PN males. Female hybrids were not affected by oophorectomy. Because castration changed disease expression only in male hybrids from the NZB female X PN male cross, it was concluded that parentage influenced sensitivity to the protective effects of male hormones. Although surgical sterilization had disparate effects on males, castrated PN/NZB and NZB/PN males consistently outlived oophorectomized females. The lack of clear-cut reversal of disease in males subjected to early castration suggested that nonhormonal, possibly genetic, factors contributed to longevity in both groups of male hybrids.     

Intake of ethanol,sodium chloride,sucrose, citric acid,and quinine hydrochloride solutions by mice: A genetic analysis

Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F₁ and F₂ hybrids were offered solutions of ethanol, sucrose, citric acid, quinine hydrochloride, and NaCl in two-bottle choice tests. Consistent with earlier work, the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride solution and less NaCl solution than did 129 mice. Analyses of each generation's means and distributions showed that intakes of ethanol, quinine, sucrose, and NaCl were influenced by a few genes. The mode of inheritance was additive in the case of ethanol and quinine, for sucrose the genotype of the 129 strain was recessive, and for NaCl it was dominant. Citric acid intake appeared to be influenced by many genes with small effects, with the 129 genotype dominant. Correlations of sucrose consumption with ethanol and citric acid consumption were found among mice of the F₂ generation, and the genetically determined component of these correlations was stronger than the component related to environmental factors. The genetically determined correlation between sucrose and ethanol intakes is consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component.     

Requirement of H-2 heterozygosity for autoimmunity in (NZB X NZW)F1 hybrid mice

In the F1 hybrid of autoimmune New Zealand Black (NZB) and phenotypically normal New Zealand White (NZW) mice, there occurs a severe systemic lupus erythematosus (SLE)-like autoimmune disease more fulminant than that found in the parental NZB mice. To determine the role of the H-2 complex in the pathogenesis of autoimmune disease of the (NZB X NZW)F1 hybrid, we developed H-2-congenic NZB (NZB.H-2z) and NZW (NZW.H-2d) strains, and compared the degree of autoimmune features between congenic H-2d/H-2d and H-2z/H-2z homozygous F1 hybrids and the original H-2d/H-2z heterozygous (NZB X NZW)F1 hybrid. We found that autoimmune features such as productions of IgG class anti-DNA antibodies and retroviral gp70 immune complexes and the development of renal disease were to a great extent reduced in both H-2 homozygous F1 hybrids, as compared with the H-2 heterozygous (NZB X NZW)F1 hybrid. It would thus appear that the heterozygosity of H-2d haplotype derived from NZB and H-2z from NZW is essential for the autoimmune disease characteristic of the (NZB X NZW)F1 hybrid.     

Ethanol intake and motor sensitization: the role of brain catalase activity in mice with different genotypes

The C57BL/6J strain of inbred mice shows a characteristic pattern of ethanol-induced behaviors: very weak acute locomotor stimulation, a lack of locomotor-sensitizing effect of ethanol, and a high level of ethanol intake. This strain has relatively low levels of activity of the ethanol metabolizing enzyme catalase, and it has been proposed that brain catalase plays a role in the modulation of some behavioral effects of ethanol. In the first study of the present paper, we investigated the effects of pharmacological manipulations of brain catalase activity on C57BL/6J mice in acute ethanol-induced locomotion and ethanol intake. Results indicated that the reduction in motor activity produced by ethanol was reversed by pretreatment with catalase potentiators and it was enhanced by catalase inhibitors. In addition, ethanol intake was highly correlated with brain catalase activity in mice treated with a catalase potentiator. In the second study, F1 hybrid mice (SWXB6) from the outbred Swiss-Webster mice and the inbred C57BL/6J mice were used. Basal brain catalase activity levels of F1 mice were intermediate between to those of the two progenitor genotypes. That profile of catalase activity was parallel to the acute-ethanol-induced locomotion and to repeated-ethanol-induced motor sensitization effects observed across the three types of mice. These data suggest that brain catalase activity modifications in the C57BL/6J strain change the pattern of several ethanol-related behaviors in this inbred mouse.     

Genetic variance contributes to ingestive processes: a survey of eleven inbred mouse strains for fat (Intralipid) intake

Genetic variation across inbred and outbred mouse strains have been observed for intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our laboratory recently reported marked strain differences in the amounts and/or percentages of kilocalories of sucrose consumed among 11 inbred and one outbred mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%) in two-bottle 24-h preference tests. To assess whether differences in fat intake were similarly associated with genetic variation, the present study examined intake of chow, water and an emulsified fat source (Intralipid) across nine different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse strains using two-bottle 24-h preference tests, which controlled for Intralipid concentration presentation effects, Intralipid and water bottle positions, and measurement of kilocalorie intake consumed as Intralipid or chow. Strains displayed differential increases in Intralipid intake relative to corresponding water with significant effects observed at the seven (BALB/cJ: 0.001% threshold sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity), three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J, C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed significantly more at the three highest concentrations to a greater degree than BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong (h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted Intralipid intake at those concentrations (0.001-1%) that displayed the largest strain-specific effects in sensitivity to Intralipid. The identification of strains with diverging abilities to regulate kilocalorie intake when presented with high Intralipid concentrations may lead to the successful mapping of genes related to hedonics and obesity.     

Motor activity and alcohol: Genetic analysis in the mouse

A genetic analysis of alcohol-induced modification of basal activity level was conducted in two strains of inbred mice, their reciprocal F₁ hybrids, and seven of their recombinant inbred (RI) strains. Alcohol induced a progressive and persistent decline in basal activity level in all of the 11 strains examined. However, the degree and extent of decline in activity varied significantly with particular progenitor or RI strains. Based on this distinct response of the various strains, a strain distribution pattern (SDP) was obtained, followed by testing of congenic line, B6.C-H-16^c. Results of the latter testing indicated that alcohol modification of basal activity is controlled by at least one locus designated Eam (ethanol activity modifier) with Eam^h designating the high decrement in activity and similar to the C57BL/6By progenitor, and Eam¹ designating the low decrement in activity and similar to the BALB/cBy progenitor. The locus is found on chromosome 4 (LG VIII) adjacent to the Exa locus which exerts a major influence on basal exploratory activity.     

Strain distribution of mice in discriminated Y-maze avoidance learning: genetic and procedural differences

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57 x SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57 x SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task.