Showing papers in "Behavior Genetics in 1993"

A test of the equal-environment assumption in twin studies of psychiatric illness.

Abstract: The traditional twin method is predicated on the equal-environment assumption (EEA)--that monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their exposure to environmental events of etiologic importance for the trait under study. In 1968, Scarr proposed a test of the EEA which examines the impact of phenotypic similarity in twins of perceived versus true zygosity. We apply this test for the EEA to five common psychiatric disorders (major depression, generalized anxiety disorder, phobia, bulimia, and alcoholism), as assessed by personal interview, in 1030 female-female twin pairs from the Virginia Twin Registry with known zygosity. We use a newly developed model-fitting approach which treats perceived zygosity as a form of specified familial environment. In 158 of the 1030 pairs (15.3%), one or both twins disagreed with the project-assigned zygosity. Model fitting provided no evidence for a significant influence of perceived zygosity on twin resemblance for any of the five disorders. Although limited in power, these results support the validity of the EEA in twin studies of psychiatric disorders.

Is the gender difference in mental rotation disappearing

Abstract: Several investigators have used meta-analysis to compare the results of studies of gender differences on various spatial tests and have concluded that the magnitude of the gender difference in spatial ability is decreasing over time. The present study used meta-analytic techniques to compare the effect size (d) of the gender difference in 14 studies published from 1975 to 1992 which administered the Mental Rotations test to adolescents and young adults. Males scored significantly higher than females in all the studies. Analyses of thed's computed for the studies revealed that the magnitude of the gender difference on the mental Rotations test has remained stable over time. Neither the Pearson correlation relating thed's to the publication dates of the studies nor the Z test of the linear contrast relating the publication dates of hte studies to the effect sizes showed a linear change in the size of the gender difference over time. The finding of a stable gender difference on the Mental Rotations test argues against the general conclusion that the gender difference in spatial ability is decreasing.

Selective breeding for alcohol preference and associated responses.

Abstract: Selective breedng for high and low alcohol-drinking preference has produced rat lines useful for studying the nature of excessive alcohol-seeking behavior. Compared with the alcohol-nonpreferring line, the preferring animals exhibit heightened responsivity to the low-dose activating effects of ethanol as well as enhanced capacity for developing tolerance to the aversive, behaviorally impairing effects of ethanol. The preferring animals exhibit lower brain serotonin and dopamine neurotransmitter activity as well as differences in other neurotransmitter neuromodulator systems, compared with the alcoholnonpreferring animals.

Testing hypotheses about direction of causation using cross-sectional family data

Abstract: We review the conditions under which cross-sectional family data (e.g., data on twin pairs or adoptees and their adoptive and biological relatives) are informative about direction of causation. When two correlated traits have rather different modes of inheritance (e.g., family resemblance is determined largely by family background for one trait and by genetic factors for the other trait), cross-sectional family data will allow tests of strong unidirectional causal hypotheses (A and B are correlated “because of the causal influence of A on B” versus “because of the causal influence of B on A”) and, under some conditions, also of the hypothesis of reciprocal causation. Possible sources of errors of inference are considered. Power analyses are reported which suggest that multiple indicator variables will be needed to ensure adequate power of rejecting false models in the presence of realistic levels of measurement error. These methods may prove useful in cases where conventional methods to establish causality, by intervention, by prospective study, or by measurement of instrumental variables, are infeasible economically, ethically or practically.

Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

Abstract: The alcohol-flush reaction occurs in Asians who inherit the mutant ALDH2*2 allele that produces an inactive aldehyde dehydrogenase enzyme. In these individuals, high blood acetaldehyde levels are believed to be the cause of the unpleasant symptoms that follow drinking. We measured the alcohol elimination rates and intensity of flushing in Chinese subjects in whom the alcohol dehydrogenase ADH2 and ALDH2 genotypes were determined. We also correlated ADH2, ADH3, and ALDH2 genotypes with drinking behavior in 100 Chinese men. We discovered that ADH2*2 and ADH3*1, alleles that encode the high activity forms of alcohol dehydrogenase, as well as the mutant ALDH2*2 allele were less frequent in alcoholics than in controls. The presence of ALDH2*2 was associated with slower alcohol metabolism and the most intense flushing. In those homozygous for ALDH2*1, the presence of two ADH2*2 alleles correlated with slightly faster alcohol metabolism and more intense flushing, although a great deal of variability in the latter was noted.

A third source of developmental differences

Abstract: An illustrative list is presented of human and animal studies which each point to the existence of a third source, in addition to genetic and environmental factors, underlying phenotypic differences in development. It is argued that this third source may consist of nonlinear epigenetic processes that can create variability at all phenotypical-somatic and behavioral-levels. In a quantitative genetic analysis with human subjects, these processes are confounded with within-family environmental influences. A preliminary model to quantify these influences is introduced.

Sensation seeking in opposite-sex twins: an effect of prenatal hormones?

Abstract: Intrauterine hormones and position with respect to male and female littermates influence sexually dimorphic adult behavior in litter-bearing animals. Opposite-sex dizygotic twins offer the opportunity to examine analogous effects on sex-related human behaviors. To illustrate this approach, Sensation Seeking Scale (SSS) scores from 422 British twin pairs, including 51 opposite-sex pairs (Zuckerman, M.,et al., J. Consult. Clin. Psychol. 46:139–149, 1978), were reanalyzed. Zuckermanet al. (1978) have shown that some aspects of sensation seeking are consistently increased in males relative to females. In comparing age-adjusted data for opposite and same-sex twins, our reanalysis demonstrated the predicted increase in sensation seeking in female members of opposite-sex pairs. Results were significant for measures of disinhibition, experience seeking, and overall sensation seeking. In contrast, male opposite-sex twins were not significantly different from male same-sex twins. Although psychosocial explanations of the increased sensation seeking in opposite-sex female twins cannot be excluded, these findings are consistent with hypothesizedin utero hormonal influences on later behavioral development.

Analyzing twin resemblance in multisymptom data: Genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys

Abstract: A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype × environment interaction (G×E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8-to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two “four-class” models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk (“predisposing”) environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple “unidimensional” model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered.

Quantitative Trait Loci (QTL) Applications to Substances of Abuse: Physical Dependence Studies with Nitrous Oxide and Ethanol in BXD Mice

Abstract: Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci—those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.

Familiality of female and male homosexuality

Abstract: We examined data from a large cohort of homosexual and heterosexual females and males concerning their siblings' sexual orientations. As in previous studies, both male and female homosexuality were familial. Homosexual females had an excess of homosexual brothers compared to heterosexual subjects, thus providing evidence that similar familial factors influence both male and female homosexuality. Furthermore, despite the large sample size, homosexual females and males did not differ significantly from each other in their proportions of either homosexual sisters or homosexual brothers. Thus, results were most consistent with the possibility that similar familial factors influence male and female sexual orientation. However, because results conflicted with those of some other studies, and because siblings' sexual orientations were obtained in a manner likely to yield more errors than in these other, smaller studies, further work is needed using large samples and more careful methods before the degree of cofamiliality of male and female homosexuality can be resolved definitively. We also examined whether some parental influences comprised shared environmental effects on sexual orientation. Scales attempting to measure such influences failed to distinguish subjects with homosexual siblings from subjects with only heterosexual siblings and, thus, did not appear to measure shared environmental determinants of sexual orientation.

The D2 dopamine receptor gene: A review of association studies in alcoholism

Abstract: Following our initial observation that the Al allele of the D2 dopamine receptor (DRD2) gene was associated with alcoholism, a number of studies, both in the United States and abroad, have attempted to replicate and extend this finding in different Caucasian populations. In nine independent studies containing a total of 491 heterogeneous alcoholics (less severe and severe) and 495 heterogeneous controls (assessed and unassessed for alcoholism), the prevalence of the Al allele was 43.0% in the former group compared to 25.7% in the latter group (odds ratio = 2.18, p < 10(-7)). The prevalence of the Al allele increased to 56.3% in a more homogeneous sample of 158 severe alcoholics (odds ratio = 3.32, p < 10(-8)). Moreover, the Bl allele of the DRD2 gene was also found to be significantly associated with severe alcoholism. Additional data are accruing which also implicate the DRD2 Al and Bl alleles in substance use disorders other than alcoholism. If further studies continue to support the results currently at hand, they would indicate that the DRD2 gene is the most prominent single gene determinant of susceptibility to severe substance abuse. However, the larger role still appears to be played by a combination of environmental factors and as yet unidentified genes.

Learning in inbred mice: Strain-specific abilities across three radial maze problems

Abstract: Mice belonging to the C57BL/6, DBA/2 (DBA), and C3H/He (C3H) strains were compared in three different eight0arm radial maze tasks requiring various degrees of spatial and nonspatial information processing. The results show that, on the standard radial maze task, C57 performed better than DBA, which, in turn, performed better than C3H. Fewer differences in the four-baited arm task and no difference in the cued version task were found between C57 and DBA, while C3H still performed more poorly. The high performance shown by C57 mice in all problems seems to be related to their ability to build up maze-running patterns based upon an optimal proportion of 45° angle turns, according to the demand of the situation. The cognitive and discriminative mechanisms involved in the solving of each task, the sensorial characteristics of the three strains, and the limits of an approach based upon neuroanatomical-behavioral correlations are discussed.

Quantitative trait loci (QTL) analyses and alcohol-related behaviors

Abstract: Recombinant inbred (RI) strains can make an important contribution toward the merger of molecular genetics and quantitative genetics in the quest for quantitative trait loci (QTL). We present preliminary analyses of alcohol-related processes from our ongoing research using the BXD RI series. Issues concerning reliability, genetic correlations, and RI QTL analysis are discussed. Several strategies for replication and extension of QTL candidate regions are considered: F1 crosses between RI strains, F2 crosses, heterogeneous stock, interspecific backcrosses, QTL selection, and the use of murine QTL in chromosomal regions syntenic to human chromosomes as candidate chromosomal regions for human QTL.

Estimating and controlling for the effects of volunteer bias with pairs of relatives

Abstract: If pairs of relatives correlate in their liability to participate in a research project, it is possible to test for the effects of volunteering on the criterion variable of interest. Much of the information for this test comes from a difference in criterion variable mean between individuals with and those without a cooperative relative. Also, if data are available from more than one class of relative, it may be possible to discriminate between (i) volunteering that occurs as a consequence of the criterion variable and (ii) volunteering as a cause of the criterion. Likelihood formulae are presented that permit quantification and significance testing of volunteer bias. If data are collected from a genetically informative design such as a twin study, it is possible to estimate genetic and environmental parameters independent of the contaminating effects of such bias. We describe some methods of reducing the computational burden of multidimensional integration to allow extension to multivariate data. Implications for research design and management are discussed.

Inheritance of predisposition to catalepsy in mice

Abstract: “Pinch-induced” catalepsy (excessive freezing) was studied in mice of nine inbred strains. The CBA/Icg strain had the highest predisposition to catalepsy, with 56% males and 73% females exhibiting 120-s immobility after four tests. A Mendelian analysis of predisposition to catalepsy was performed on CBA/Icg and AKR/J mice contrasting in this trait. Reciprocal F1 hybrids did not display freezing after 10 tests. The number of cataleptic and noncataleptic animals among the F2's and in the families of the CBA×F2 backcrosses agreed with the hypothesis that the pronounced predisposition to catalepsy in the CBA/Icg mice was determined by a single autosomal locus in homozygous recessive condition.

Selective breeding for alcohol withdrawal severity.

Abstract: Mouse lines have been genetically selected to be alcohol Withdrawal Seizure Prone (WSP) or Resistant (WSR). The selection index is the severity of withdrawal handling-induced convulsions seen after removal of mice from chronic exposure to ethanol vapor. Behavioral, pharmacological, and neurochemical results from a replicated bidirectional selection project are reviewed. In reciprocal F1 crosses of the WSP and WSR lines, substantial dominance for resistance to withdrawal was found in both replicated sets of lines. WSP and WSR mice differ principally, and markedly, in traits related to the severity of withdrawal from alcohols and other drugs with depressant properties. This suggests that genes influencing severity of withdrawal from chronic ethanol exposure also pleiotropically influence genetic susceptibility to dependence on other drugs of abuse. However, the results of WSP vs. WSR comparisons for traits related to ethanol sensitivity and tolerance development suggest control in large part by genes different from those influencing withdrawal severity.

Segregation analysis of speech and language disorders

Abstract: Complex segregation analysis was performed on pedigrees ascertained through 45 probands (26 males, 19 females) with a history of preschool speech and language disorders. Hypotheses concerning mode of inheritance were, tested using the POINTER segregation analysis program. Although there is strong evidence for familial transmission of this trait, we were unable to distinguish between a major gene and multifactorial transmission model using likelihood-ratio chi-square tests. Future studies with quantitative measures of speech and language disorders are needed to resolve the issue of mode of inheritance for this trait.

Genetic analysis of different kinds of aggressive behavior.

Abstract: Various kinds of aggressive behavior such as spontaneous intermale aggression, predatory aggression (locust-killing behavior), and irritable (shock-induced) aggression were investigated in inbred strains of mice. Genotype was shown to affect significantly the phenotypic variety of these kinds of aggression. There were, however, no interstrain correlations either between intermale aggression and predatory behavior or between intensity of intermale, shock-induced aggression and locust-killing behavior. Moreover, the intermale aggression level (percentage of fighting mice in each strain) did not correlate with the intensity of fighting. It has been shown by Mendelian analysis on C57BL/6J and BALB/c strains that these indices of intermale aggression are under different genetic control. The selection of Norway rats over 20 generations for reduced fear-induced aggressiveness toward man resulted in a decrease in irritable aggression and loss of an aggressive response to man. No changes in intermale and predatory aggression, however, were found. Hence, different kinds of aggressive behavior—intermale, predatory, and fear-induced aggression—seem to be controlled by different genetic mechanisms.

Selective breeding for initial sensitivity to ethanol.

Abstract: Selective breeding for initial sensitivity to ethanol has been carried out by a number of investigators in order to investigate the mechanisms by which ethanol brings about a myriad of effects on the mammalian central nervous system. In addition the availability of these selectively bred animals provides clues to the causes of the genetic predisposition of humans to alcoholism. Eventually it is envisioned that the synteny between the mouse and human genomes will allow identification of specific genes responsible for acute effects of ethanol in both species as well as clues as to how alcoholism in humans can be better identified, prevented, and treated.

Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells

Abstract: Ethanol, acutely, is a potent and selective inhibitor of the function of theN-methyl-d-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured by ligand binding) is increased in many brain areas. Similarly, NMDA receptor function is increased in cerebellar granule cells exposed chronically to ethanol. In the intact animal, this receptor up-regulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In contrast to ethanol, barbiturates have a greater inhibitory effect at the kainate subtype of glutamate receptor than at the NMDA receptor. After chronic barbiturate ingestion, kainate binding isdecreased in certain brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates on NMDA and kainate receptor function is quite distinct from that of ethanol.

Genetic mediation of infanticide and parental behavior in male and female domestic and wild stock house mice.

Abstract: Infanticide is a reproductive strategy found in many mammals, especially rodents. The proportion of male and female house mice (Mus domesticus) that are either infanticidal or noninfanticidal is strain specific and varies widely from stock to stock. Male house mice also show strain-specific variation in the behavioral mechanisms that inhibit infanticidal individuals from killing their own offspring. The adult offspring generated from reciprocally crossed CF-1 and Wild stock house mice were tested for their behavior toward newborn pups. In male CF-1xWild hybrids, the proportion of infanticidal and noninfanticidal males matched with their maternal phenotype, whereas female CF-1xWild hybrids exhibited a proportion of behaviors typical of the CF-1 phenotype, regardless of their mother's genotype. Our results suggest three conclusions: first, that infanticide is a highly labile and heritable behavior in both sexes; second, that there is a sex difference in the genetic substrate that regulates the inheritance of infanticidal behavior; and third, that selection pressures in male mice may operate independently on the mechanisms that promote spontaneous infanticidal behavior versus the mechanisms that inhibit infanticide.

Elevated dark-adapted thresholds in hypopigmented mice measured with a water maze screening apparatus.

Abstract: In previous electrophysiological experiments from hypopigmented animals (mice, rats, rabbits), single-unit recordings from both retinal ganglion axons and cells in the superior colliculus have demonstrated an increase in threshold in the dark-adapted state which is roughly proportional to the ocular melanin concentration. In the present study we compared an albino mouse strain which is relatively resistant to light damage and the beige mouse mutant to their wild-type controls in a situation that involved unanesthetized, unrestrained mice as a control to the electrophysiological single unit experiments. We used a six-chambered water maze. Animals were trained to swim to an illuminated ramp until their performances leveled off (about 10 days). The animals were then dark-adapted for 24 h and tested after reducing the luminance level of the water maze. We found that the albino mice failed to find the ramp when the luminance fell to 1.58×10−3 cd/m2 (p≤.0001), the beige mice failed at 2.00×10−4 cd/m2 (p≤.0001), and the normally pigmented controls performed to 5.00×10−5 cd/m2 (p≤.0001). These results support our previous findings that the sensitivity defect in hypopigmented animals is proportional to the degree of ocular hypopigmentation.

Identification of stimuli that mediate experience-dependent modification of homosexual courtship in Drosophila melanogaster

Abstract: A naive, sexually mature D. melanogaster male tested with a young, sexually immature male will perform vigorous courtship, but the mature male will perform much less courtship if he is subsequently tested with a second young male. This phenomenon is called experience-dependent courtship modification (EDCM). We have shown that exposure to either or both of the two courtship-stimulating pheromones that immature males synthesize is sufficient to induce EDCM.

A comparison of the contribution of the major histocompatibility complex (MHC) and Y chromosomes to the discriminability of individual urine odors of mice by Long-Evans rats.

Abstract: A go/no-go operant task was used to assess the ability of male Long-Evans rats to discriminate between the urine odors from pairs of intact MHC congenic mice (C57BL/6-H-2Kb/J and C57BL/6-H-2Kbm1/ByJ), intact Y congenic mice (DBA1 and DBA1.C57BL10-Y), and castrated Y congenic mice of these two strains. The MHC congenic strains differ in alleles of the H-2 K locus, while the Y congenic strains differ in the nonrecombining part of the Y chromosome. Analysis of the number of correct responses to a criterion of 85% correct on each block of 20 trials revealed that the ability of the subjects to discriminate between urine odors did not differ whether samples were from pairs of intact MHC congenic mice, intact Y congenic mice, or castrated Y congenic mice. These findings are consistent with the hypothesis that individually unique urine odors may be influenced both by genes in the nonrecombining part of the Y chromosome and by genes in the major histocompatibility complex of chromosome 17. These odors are not androgen dependent. Such urinary chemical signals may be involved in pregnancy block (the Bruce effect), aggression, and other mouse social behaviors.

Differences in heritability across groups differing in ability, revisited

Abstract: Three recent studies have used twin data to explore the possibility of differential contributions of heritability and environmentality to individual differences in cognitive ability as a function of ability level (Detterman, D. K.,et al., Behav. Genet. 20:369–384; 1990; Bailey, M. J. amd Revelle, W.,Behav. Genet. 21:397–404, 1991; Cherny, S. S.,et al., Behav. Genet. 22:153–162, 1992). All arrived at different conclusions: higher heritability at the low end, higher heritability at the high end, and no differential influence, respectively. The current report involves a sample of 148 identical and 135 fraternal twin pairs from the Western Twin Project who were tested on a battery of intelligence and achievement tests to further explore the issue. The results suggest no significant differences in heritability at either the high or the low end, although a trend toward higher heritability for children of higher ability is evident. Individual differences for a composite ability/achievement score showed significantly greater influence of shared family environment at the low end than the rest of the distribution. In general, results for cognitive ability and academic achievement were highly similar.

Selection for high and low pupation height in Drosophila ananassae.

Abstract: Selection for high and low pupation height in Drosophila ananassae was carried out for 10 generations. Response to selection resulted in rapid divergence in pupation height in replicates of both high and low lines. There was a significant difference in mean pupation height among high, low, and control lines. Regression coefficients for both high and low lines were significantly different from zero. The realized heritability over 10 generations was 45-49 for the high lines and 26-29 for the low lines. The F1 hybrids produced by making reciprocal crosses between high and low lines showed intermediate pupation height. These findings suggest that pupation height in D. ananassae is under polygenic control, with a substantial amount of additive genetic variation.

Evolutionary adaptation and stress: Energy budgets and habitats preferred

Abstract: Natural populations are normally exposed to substantial environmental stress. The consequences of stress include elevated metabolic costs and additive genetic variability. From the former, preferred habitats should be located in environments corresponding to minimum total energy expenditure. This tendency occurs in the field for behavioral adaptation ofDrosophila to variable temperature (and humidity) conditions. Laboratory studies of resource preference inDrosophila suggest a low genetic variability. However, under more stressful field conditions, genetic variability should be higher. Habitat preference studies under stressful conditions therefore need to be emphasized in modeling situations in nature.

Neurological dysfunction expressed in the grooming behavior of developing weaver mutant mice

Abstract: The present study provides the first quantitative developmental analysis of movement in the weaver (wv/wv) mutant mouse. This autosomal recessive mutation affects both striatal and cerebellar circuitries that are related to motor performance. We report data on postswim grooming behavior in 14 mutant and 14 control animals on alternate postnatal Days 13–20. Mutant animals showed a greater number, but shorter duration, of grooming bouts across this developmental period. The mutant animals also used external support during grooming, expressed various forms of ataxia, performed a higher proportion of smaller forelimb strokes than did the control animals, and failed to complete as many full stereotypic grooming sequences. These differences between mutant and control animals followed distinctive developmental courses. Our data demonstrate that previous anatomical and physiological characterizations of the weaver mutation have overt motor correlates.