Calcium taste preferences: genetic analysis and genome screen of C57BL/6J x PWK/PhJ hybrid mice

To characterize the genetic basis of voluntary calcium consumption, we tested C57BL/6J mice (B6; with low avidity for calcium), PWK/PhJ mice (PWK; with high avidity for calcium) and their F₁ and F₂ hybrids. All mice received a series of 96-h two-bottle preference tests with a choice between water and the following: 50 m m CaCl₂, 50 m m calcium lactate, 50 m m MgCl₂, 100 m m KCl, 100 m m NH₄Cl, 100 m m NaCl, 5 m m citric acid, 30 μ m quinine hydrochloride and 2 m m saccharin. Most frequency distributions of the parental and F₁ but not F₂ groups were normally distributed, and there were few sex differences. Reciprocal cross analysis showed that B6 × PWK F₁ mice had a non-specific elevation of fluid intake relative to PWK × B6 F₁ mice. In the F₂ mice, trait correlations were clustered among the divalent salts and the monovalent chlorides. A genome screen involving 116 markers showed 30 quantitative trait loci (QTLs), of which six involved consumption of calcium chloride or lactate. The results show pleiotropic controls of calcium and magnesium consumption that are distinct from those controlling consumption of monovalent chlorides or exemplars of the primary taste qualities.     

C57BL/6J and DBA/2J mice vary in lick rate and ingestive microstructure

Fluid licking in mice is an example of a rhythmic behavior thought to be under the control of a central pattern generator. Inbred strains of mice have been shown to differ in mean or modal interlick interval (ILI) duration, suggesting a genetic-based variation. We investigated water licking in the commonly used inbred strains C57BL/6J (B6) and DBA/2J (D2), using a commercially available contact lickometer. Results from 20-min test sessions indicated that D2 mice lick at a faster rate than B6 mice (10.6 licks/s vs. 8.5 licks/s), based on analysis of the distribution of short-duration ILIs (50-160 ms). This strain difference was independent of sex, extent of water deprivation or total number of licks. D2 mice also displayed a faster lick rate when the strains were tested with a series of brief (5 s) trials. However, when ingestion over the entire 20-min session was analyzed, it was evident that D2 mice had an overall slower rate of ingestion than B6 mice. This was because of the tendency for D2 mice to have more very long pauses (>30 s) between sequences of licking bursts. Overall, it appeared that D2 mice licked more efficiently, ingesting more rapidly during excursions to the spout that were fewer and farther between.     

Chromosomal loci that influence oral nicotine consumption in C57BL/6J x C3H/HeJ F2 intercross mice

Several studies have demonstrated that there are genetic influences on free-choice oral nicotine consumption in mice. In order to establish the genetic architecture that underlies individual differences in free-choice nicotine consumption, quantitative trait loci (QTL) mapping was used to identify chromosomal regions that influence free-choice nicotine consumption in male and female F(2) mice derived from a cross between C57BL/6J and C3H/HeJ mice. These two mouse strains were chosen not only because they differ significantly for oral nicotine consumption, but also because they are at or near phenotypic extremes for all measures of nicotine sensitivity that have been reported. A four-bottle choice paradigm was used to assess nicotine consumption over an 8-day period. The four bottles contained water or water supplemented with 25, 50 or 100 microg/ml of nicotine base. Using micrograms of nicotine consumed per milliliter of total fluid consumed per day as the nicotine consumption phenotype, four significant QTL were identified. The QTL with the largest LOD score was located on distal chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL appear to be responsible for up to 62% of the phenotypic variance in oral nicotine consumption.     

Latent inhibition and extinction of passive avoidance in mice C57BL/6J AND DBA/2J

The study was carried out in mice C57BL/6J and DBA/2J for comparative analysis of two interference processes: latent inhibition and extinction of passive avoidance produced with an unconditioned aversive stimulus of different parameters (0.5 and 0.25 mA). With a strong training to new stimulus, impairment of extinction has been detected only in mice DBA/2J. Reduction in the strength of punishment during training was accompanied by acceleration of extinction in mice C57BL/6J and its appearance in mice DBA/2J. The learning of passive avoidance in strong and weak reinforcement was the same for both strains of mice. Interline differences were found also in the analysis of latent inhibition. With strong and weak training to conditional stimulus, lost of novelty by repeated an 8-fold pre-exposures to the experimental chamber, in DBA/2J mice, in contrast to C57BL/6J, latent inhibition was disrupted. In addition, DBA/2J mice showed impairment of extinction with weak training to non-relevant stimulus.     

Genetic control of sex-chromosomal univalency in the spermatocytes of C57BL/6J and DBA/2J mice

The genetic control of sex-chromosomal univalency was examined in the primary spermatocytes of the mouse. The C57BL/6J strain expresses 3% X-Y univalency and DBA/2J expresses 37% univalency. The reciprocal F1 and the eight types of reciprocal backcross males were examined. In the C57BL/6J--DBA/2J strain pair, X--Y univalency is controlled by three genetic systems. Autosomal factors of unknown number that are dominant in DBA/2J increase the probability of univalency from 3% in C57BL/6J to 12%. The DBA/2J-Y chromosome, in place of the C57BL/6J-Y chromosome, has an additive effect to increase the probability of univalency from 12 to 37% in the DBA/2J strain. Two X-chromosome factors that differ between C57BL/6J and DBA/2J regulate the probability of univalency. The X-chromosome factors appear to be separated by sufficient distance so that, with the DBA/2J-Y chromosome and dominant DBA/2J autosomal factors, there are two recombinant classes of X--Y univalency at 20 and 60%. The genetic factors in the univalency trait may be involved in the regulation or structure of the terminal attachment sites between the X and Y chromosomes.     

A genome-wide set of congenic mouse strains derived from DBA/2J on a C57BL/6J background

In the analysis of complex traits, congenic strains are powerful tools because they allow characterization of a single locus in the absence of genetic variation throughout the remainder of the genome. Here, we report the construction and initial characterization of a genome-wide panel of congenic strains derived from the donor strain DBA/2J on the background strain C57BL/6J. For many strains, we have carried out high-density SNP genotyping to precisely map the congenic interval and to identify any contaminating regions. Certain strains exhibit striking variation in litter size and in the ratio of females to males. We illustrate the utility of the set by "Mendelizing" the complex trait of myocardial calcification. These 65 strains cover more than 95% of the autosomal genome and should facilitate the analysis of the many genetic trait differences that have been reported between these parental strains.     

QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects

Baseline serum hematocrit varies substantially in the population. While additive genetic factors account for a large part of this variability, little is known about the genetic architecture underlying the trait. Because hematocrit levels vary with age, it is plausible that quantitative trait loci (QTL) that influence the phenotype also show an age-specific profile. To investigate this possibility, hematocrit was measured in three different age cohorts of mice (150, 450, and 750 days) of the C57BL/6J (B6) and the DBA2/J (D2) lineage. QTL were searched in the B6D2F₂ intercross and the BXD recombinant inbred (RI) strains. The effects of these QTL were explored across the different age groups. On the phenotypic level, baseline serum hematocrit declines with age in a sex-specific manner. In the B6D2F₂ intercross, suggestive QTL that influence the phenotype were located on Chromosomes (Chr) 1, 2, 7, 11, 13, and 16. With the exception of the QTL on Chr 2, all of these QTL exerted their largest effect at 750 days. The QTL on Chr 1, 2, 7, 11 and 16 were confirmed in the BXD RIs in a sex- and age-specific manner. Linkage analysis in the BXD RIs revealed an additional significant QTL on Chr 19. Baseline serum hematocrit is influenced by several QTL that appear to vary with the age and sex of the animal. These QTL primarily overlap with QTL that have been shown to regulate hematopoietic stem cell phenotypes.     

Evaluating gene expression in C57BL/6J and DBA/2J mouse striatum using RNA-Seq and microarrays

C57BL/6J (B6) and DBA/2J (D2) are two of the most commonly used inbred mouse strains in neuroscience research. However, the only currently available mouse genome is based entirely on the B6 strain sequence. Subsequently, oligonucleotide microarray probes are based solely on this B6 reference sequence, making their application for gene expression profiling comparisons across mouse strains dubious due to their allelic sequence differences, including single nucleotide polymorphisms (SNPs). The emergence of next-generation sequencing (NGS) and the RNA-Seq application provides a clear alternative to oligonucleotide arrays for detecting differential gene expression without the problems inherent to hybridization-based technologies. Using RNA-Seq, an average of 22 million short sequencing reads were generated per sample for 21 samples (10 B6 and 11 D2), and these reads were aligned to the mouse reference genome, allowing 16,183 Ensembl genes to be queried in striatum for both strains. To determine differential expression, 'digital mRNA counting' is applied based on reads that map to exons. The current study compares RNA-Seq (Illumina GA IIx) with two microarray platforms (Illumina MouseRef-8 v2.0 and Affymetrix MOE 430 2.0) to detect differential striatal gene expression between the B6 and D2 inbred mouse strains. We show that by using stringent data processing requirements differential expression as determined by RNA-Seq is concordant with both the Affymetrix and Illumina platforms in more instances than it is concordant with only a single platform, and that instances of discordance with respect to direction of fold change were rare. Finally, we show that additional information is gained from RNA-Seq compared to hybridization-based techniques as RNA-Seq detects more genes than either microarray platform. The majority of genes differentially expressed in RNA-Seq were only detected as present in RNA-Seq, which is important for studies with smaller effect sizes where the sensitivity of hybridization-based techniques could bias interpretation.     

Substrain specific behavioral responses in male C57BL/6N and C57BL/6J mice to a shortened 21-hour day and high-fat diet

ABSTRACT

Altered circadian rhythms have negative consequences on health and behavior. Emerging evidence suggests genetics influences the physiological and behavioral responses to circadian disruption. We investigated the effects of a 21 h day (T = 21 cycle), with high-fat diet consumption, on locomotor activity, explorative behaviors, and health in male C57BL/6J and C57BL/6N mice. Mice were exposed to either a T = 24 or T = 21 cycle and given standard rodent chow (RC) or a 60% high-fat diet (HFD) followed by behavioral assays and physiological measures. We uncovered numerous strain differences within the behavioral and physiological assays, mainly that C57BL/6J mice exhibit reduced susceptibility to the obesogenic effects of (HFD) and anxiety-like behavior as well as increased circadian and novelty-induced locomotor activity compared to C57BL/6N mice. There were also substrain-specific differences in behavioral responses to the T = 21 cycle, including exploratory behaviors and circadian locomotor activity. Under the 21-h day, mice consuming RC displayed entrainment, while mice exposed to HFD exhibited a lengthening of activity rhythms. In the open-field and light-dark box, mice exposed to the T = 21 cycle had increased novelty-induced locomotor activity with no further effects of diet, suggesting daylength may affect mood-related behaviors. These results indicate that different circadian cycles impact metabolic and behavioral responses depending on genetic background, and despite circadian entrainment.     

Oral amiloride treatment decreases taste sensitivity to sodium salts in C57BL/6J and DBA/2J mice

Sodium taste transduction is thought to occur via an amiloride-sensitive, sodium-selective pathway and an amiloride-insensitive, cation nonselective, anion-dependent pathway(s). It has been shown by others that amiloride, an epithelial sodium channel (ENaC) blocker, significantly reduces the chorda tympani nerve response to lingually applied NaCl in C57BL/6 (B6) mice but not in DBA/2 (D2) mice, suggesting that the latter strain might not possess functional ENaCs in taste receptor cells. We psychophysically measured and compared taste detection thresholds of NaCl and sodium gluconate (NaGlu) prepared with and without 100 microM amiloride in these two strains (eight/strain). Mice were trained and tested in a two-response operant signal detection procedure conducted in a gustometer. Surprisingly, no strain effect was found for the detection thresholds of both salts (approximately 0.05-0.06 M). Moreover, these thresholds were increased by almost an order of magnitude by amiloride adulteration of the solutions. This marked effect of amiloride on sodium detection thresholds suggests that ENaCs are necessary for normal sensitivity to sodium salts in both strains. In addition, because NaGlu is thought to stimulate primarily the amiloride-sensitive pathway, especially at low concentrations, the similarity of NaCl and NaGlu thresholds (r > 0.81 both strains) suggests that ENaCs are also sufficient to support the detection of sodium in weak solutions by B6 and D2 mice.     

Metabolomic analysis of liver and skeletal muscle tissues in C57BL/6J and DBA/2J mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to have the adverse effects on human health. In this study, we applied a metabolomic approach in conjunction with unsupervised and supervised machine learning methods to investigate the toxic effects of TCDD. By using liquid chromatography/quadrupole time-of-flight mass spectrometry, non-targeted metabolomic analysis revealed the metabolic signatures of the toxicity in aryl hydrocarbon receptor (AhR)-high affinity C57BL/6J (C6) mice as well as low affinity strain-DBA/2J (D2) mice. Lysophospholipids and long chain fatty acids were strikingly elevated in the C6 mice exposed to TCDD in both liver and skeletal muscle tissues. Meanwhile, the level of palmitoylcarnitine, which is one of the important indicators in fatty acid β-oxidation, increased significantly. Moreover, several nucleosides and amino acids decreased markedly. On the other hand, much less differentiating metabolites were highlighted in another strain-D2 mouse model. Taking liver and skeletal muscle tissues together, the levels of inosine, valine and glutamine decreased significantly. One lysophospholipid and two fatty acids were found to be enhanced. The principal components analysis and support vector machine clustering results also exhibited discriminations in the liver and skeletal muscle tissues of the mice. The obtained results indicated that TCDD could disrupt several metabolic pathways, including fatty acid biosynthesis and amino acid metabolism in both C6 and D2 mice. The increased rate of fatty acid beta-oxidation, however, was only observed in the liver and skeletal muscle tissues of C6 mice. The perturbation of the tricarboxylic acid (TCA) cycle was testified in two strains but the change was much slighter in D2 mice. It was of particular interest to note that the succinate level was enhanced in the liver tissues of both strains, and particularly, the change was up to 11.49-fold in the liver of C6 mice treated with TCDD. Collectively, the discrimination of D2 mice was not as distinct as that of C6 mice when exposed to the same dosage. Furthermore, D2 was confirmed to be less-sensitive rather than resistant to a high dose of TCDD.     

Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences

The aim of the present study was to investigate the effects of individual housing on mouse behavior. The male mice of the C57BL/6J and DBA/2 strains were separated at the age of 4 weeks and kept in individual housing for 7 weeks until behavioral testing began. Their behavior was compared to the group-housed mice in a battery of tests during the following 7 weeks. The single-housed mice were hyperactive and displayed reduced habituation in the tests assessing activity and exploration. Reduced anxiety was established in the elevated plus-maze, but an opposite effect was observed in the dark-light (DL) and hyponeophagia tests. Immobility in the forced swimming test was reduced by social isolation. The DBA mice displayed higher anxiety-like behavior than the B6 mice in the plus-maze and DL exploration test, but hyponeophagia was reduced in the DBA mice. Moreover, all effects of individual housing on the exploratory and emotional behavior were more evident in the DBA than in the B6 mice. Novel object recognition and fear conditioning (FC) were significantly impaired in the single-housed mice, whereas water-maze (WM) learning was not affected. Marked strain differences were established in all three learning tests. The B6 mice performed better in the object recognition and FC tasks. Initial spatial learning in the WM was faster and memory retention slightly enhanced in the B6 mice. The DBA mice displayed lower preference to the new and enhanced preference to the old platform location than the B6 mice after reversal learning in the WM. We conclude that individual housing has strong strain- and test-specific effects on emotional behavior and impairs memory in certain tasks.     

Food restriction-like effects of dietary dehydroepiandrosterone. Hypothalamic neurotransmitters and metabolites in male C57BL/6 and (C57BL/6 x DBA/2)F1 mice

Dehydroepiandrosterone (DHEA) is a precursor of sex hormones in mammals. Dietary DHEA serves to prevent or inhibit various diseases and also lengthens life spans of animals. Moreover, dietary DHEA inhibits food intake in certain strains of mice. We administered DHEA (0.45% w/w of food) to C57BL/6 (B6) and (B6 x DBA/2)F1 (BDF1) mice for 5 weeks. Food intake was inhibited in both strains of mice during the first week. Thereafter, B6, but not BDF1, mice consumed less food. Because hypothalamic serotonin and/or dopamine regulate appetite, satiety and other behaviors, the hypothesis tested was that hypothalamic concentration of serotonin, dopamine and/or their metabolites are affected differentially in B6 and BDF1 mice fed DHEA. In another study, mice were fed the AIN-76A diet with or without DHEA for 1 and 7 days or were pair-fed to DHEA-fed mice for 7 days. On Day 1 of DHEA feeding (acute effects) hypothalamic levels of serotonin, dopamine, and metabolites were unchanged in B6 mice, but levels of dopamine were increased and levels of dopamine metabolites were decreased in BDF1 mice. On Day 7 of DHEA feeding, levels of serotonin were increased in BDF1 but not B6 mice. On Day 7 of pair-feeding there were decreased levels of hypothalamic dopamine metabolites in BDF1 but not B6 mice. Paraventricular nuclei of BDF1 mice had decreased levels of serotonin but not of dopamine in all groups. Serum levels of DHEA and its metabolite, 5-androstene-3beta,17beta-diol, correlated significantly only with serotonin concentrations in BDF1 mice. The salient findings of these experiments are that DHEA inhibits food intake to a greater extent in B6 than in BDF1 mice. However, alterations of hypothalamic neurotransmitters were greater in BDF1 than in B6 mice. Because BDF1 and B6 mice share B6 genes, relevant gene(s) derived from DBA/2 mice might mediate the different responses detected.     

Amiloride is an ineffective conditioned stimulus in taste aversion learning in C57BL/6J and DBA/2J mice

The epithelial sodium channel (ENaC) blocker amiloride has been shown to increase the behaviorally measured NaCl detection threshold in mice. In this study, a conditioned taste aversion (CTA) paradigm was used to examine whether 100 microM amiloride has a perceptible taste that could contribute to this observed decrease in behavioral responsiveness. Eighty-four C57BL/6J (B6) and 64 DBA/2J (D2) mice were divided into eight groups (n=8-12 per group), in which half received an injection of 0.15 M LiCl (2 mEq/kg) and the other half an equivalent saline injection, in three conditioning trials. The four conditioned stimuli were 100 microM amiloride hydrochloride, water, 0.1 and 0.3 M NaCl. Neither strain demonstrated acquisition of a CTA to amiloride in a brief-access (BA) taste test (5 s trials in the gustometer). Although 0.3 M NaCl is inherently aversive, its pairing with LiCl led to significantly further decreases in licking during the BA test on salt trials in both strains. The D2 strain clearly avoided 0.1 M NaCl, whereas avoidance of this stimulus was more equivocal in B6 mice. The inefficacy of amiloride to serve as a conditioned stimulus in taste aversion learning involving three LiCl pairings suggests that the effects of this ENaC blocker on taste-related behavioral responses to NaCl are likely due to its pharmacological interference with sodium taste transduction.     

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

Background

The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.

Results

We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.

Conclusions

Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.     

C57BL/6小鼠性别差异对髓鞘少突胶质糖蛋白诱导的实验性自身脑脊髓炎疾病的影响

多发性硬化是人类常见的中枢神经系统自身免疫性炎症致脱髓鞘疾病．流行病学研究发现,女性患者多于男性,其平均发病时间早于男性．实验性自身免疫性脑脊髓炎(EAE)与多发性硬化症有相似的临床症状和病理特征,是被广泛应用于人类疾病研究的动物模型．本实验利用髓鞘少突胶质糖蛋白MOG_33-35免疫C57BL/6小鼠建立EAE模型,观察29天．通过疾病评分发现雌雄小鼠在发病率、起病时间上均无明显差别,但雄鼠的发病症状明显比雌鼠严重．在其病理切片HE染色中观察到雄性小鼠中枢浸润的炎性细胞多于雌性小鼠,并且在LFB染色中同样观察到雄鼠脱髓鞘区域明显增大．对其发病高峰期中枢浸润细胞的染色分析时,可以发现雄性小鼠中浸润的CD4 T细胞及其亚群T_H-1和T_H-17细胞均有明显增加．这些都表明MOG_33-35免疫C57BL/6小鼠建立的EAE模型存在着性别差异的影响,这一发现为今后建立多发性硬化症的动物模型中动物性别的选择提供了一定的参考依据．     

Effects of maternal strain on ethanol responses in reciprocal F1 C57BL/6J and DBA/2J hybrid mice

Variations in maternal behavior, either occurring naturally or in response to experimental manipulations, have been shown to exert long-lasting consequences on offspring behavior and physiology. Despite previous research examining the effects of developmental manipulations on drug-related phenotypes, few studies have specifically investigated the influence of strain-based differences in maternal behavior on drug responses in mice. The current experiments used reciprocal F1 hybrids of two inbred mouse strains (i.e. DBA/2J and C57BL/6J) that differ in both ethanol (EtOH) responses and maternal behavior to assess the effects of maternal environment on EtOH-related phenotypes. Male and female DBA/2J and C57BL/6J mice and their reciprocal F1 hybrids reared by either DBA/2J or C57BL/6J dams were tested in adulthood for EtOH intake (choice, forced), EtOH-induced hypothermia, EtOH-induced activity and EtOH-induced conditioned place preference (CPP). C57BL/6J and DBA/2J mice showed differences on all EtOH responses. Consistent with previous reports that maternal strain can influence EtOH intake, F1 hybrids reared by C57BL/6J dams consumed more EtOH during forced exposure than did F1 hybrids reared by DBA/2J dams. Maternal strain also influenced EtOH-induced hypothermic responses in F1 hybrids, producing differences in hybrid mice that paralleled those of the inbred strains. In contrast, maternal strain did not influence EtOH-induced activity or CPP in hybrid mice. The current findings indicate that maternal environment may contribute to variance in EtOH-induced hypothermia and EtOH intake, although effects on EtOH intake appear to be dependent upon the type of EtOH exposure.     

Genomic analysis of a novel spontaneous albino C57BL/6N mouse strain

We report an albino C57BL/6N mouse strain carrying a spontaneous mutation in the tyrosinase gene (C57BL/6N‐Tyr^cWTSI). Deep whole genome sequencing of founder mice revealed very little divergence from C57BL/6NJ and C57BL/6N (Taconic). This coisogenic strain will be of great utility for the International Mouse Phenotyping Consortium (IMPC), which uses the EUCOMM/KOMP targeted C57BL/6N ES cell resource, and other investigators wishing to work on a defined C57BL/6N background. genesis 51:523–528. © 2013 The Authors. Genesis Published by Wiley Periodicals, Inc.     

Comparative toxicity and biotransformation of lindane in C57BL/6 and DBA/2 mice

DBA/2 mice, previously identified as "unresponsive" to aromatic hydrocarbons which induce microsomal enzymes in C57BL/6 mice, are more vulnerable to the convulsant effect of repeated doses of lindane than similarly treated C57BL/6 mice. Death in convulsions and higher blood and brain lindane concentrations indicate that less efficient disposition of lindane itself accounts for the greater vulnerability of the DBA/2 mice. The same two principal chlorophenolic metabolites of lindane were identified in the blood and tissues of both strains, but the time-courses of blood concentrations in response to repeated lindane dosing were different.