Hot topics in behavioral and neural genetics.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S C Maxson
Publications and source records attributed to S C Maxson.
Aggressive behavioral phenotypes in mice.
Aggressive behavior in male and female mice occurs in conflicts with intruding rivals, most often for the purpose of suppressing the reproductive success of the opponent. The behavioral repertoire of fighting is composed of intricately sequenced bursts of species-typical elements, with the resident displaying offensive and the intruder defensive acts and postures. The probability of occurrence as well as the frequency, duration, temporal and sequential patterns of aggressive behavior can be quantified with ethological methods. Classic selection and strain comparisons show the heritability of aggressive behavior, and point to the influence of several genes, including some of them on the Y chromosome. However, genetic effects on aggressive behavior critically depend upon the background strain, maternal environment and the intruder. These factors are equally important in determining changes in aggressive behavior in mice with a specific gene deletion. While changes in aggression characterize mutant mice involving a variety of genes, no pattern has emerged that links particular gene products (i.e. enzyme, peptide, receptor) to either an increase or a decrease in aggressive behavior, but rather emphasizes polygenic influences. A potentially common mechanism may be some components of the serotonin system, since alterations in 5-HT neurotransmission have been found in several of the KO mice that display unusual aggressive behavior.
Aggression↗
Y chromosome, urinary chemosignals, and an agonistic behavior (offense) of mice.
In mice, offense is one type of agonistic behavior associated with attacks. Offense of male mice was measured in a panel of testers design. The mice were DBA1 (D1) and DBA1.C57BL10-Y (D1.B10-Y). These are congenic for the male-specific, nonrecombining part of the Y chromosome. For the behavioral experiments, urine from D1 or D1.B10-Y mice was daubed on gonadectomized opponents. The opponents were of two genotypes, D1 or D1.B10-Y. The experimental subjects were of the same two genotypes. There were main effects for strain of experimental subject and strain of urine donor as well as interactions for strain of experimental subject x strain of gonadectomized opponent, strain of gonadectomized opponent x strain of urine donor, and strain of experimental subject x strain of gonadectomized opponent x strain of urine donor. These findings are consistent with a model in which this part of the Y chromosome affects testosterone-dependent pheromones and non-testosterone-dependent odor types acting as motivating stimuli, the olfactory perception of motivating stimuli for offense, and the motivational mechanism for offense.
Agonistic Behavior↗
Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.
Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases.
Animals↗
Genotype-dependent sex differentiation of dopaminergic neurons in primary cultures of embryonic mouse brain.
In order to investigate genetic factors that interfere with hormone-mediated sex differentiation of dopaminergic neurons, we raised sex-specific primary cultures from embryonic day 13 diencephalon (D) or mesencephalon (M) of three different strains of mice, NMRI, CBA/J, and BALBc/J. Part of the cultures were maintained for 6 or 13 days in vitro (DIV) in medium containing 17 beta-estradiol or testosterone. The cultures were analyzed for sex differences in numbers of tyrosine hydroxylase-immunoreactive neurons, endogenous dopamine (DA) levels, and specific uptake of [3H]DA. Previous results obtained with cultures of embryonic Sprague-Dawley rats had shown that these parameters develop sex-specific characteristics in the absence of sex differences in hormone environment. Similar steroid-independent sex differences as they occur in the rat were found in M cultures of NMRI but not in CBA and BALBc mice. Long-term sex steroid treatment did not affect any of the above parameters in any strain. It is concluded that cell-autonomous realization of the genetic sex of dopaminergic neurons depends on the genetic background.
Analysis of Variance↗
Issues in the search for candidate genes in mice as potential animal models of human aggression.
Conceptual and methodological issues in the search for candidate genes for mouse aggression and for the development of animal models of human aggression are considered. First, the focus is on genetic and then behavioural aspects of the search for candidate genes in mice. For the genetic aspect, two approaches are presented. In mice, these are chromosome mapping of polymorphic genes and evaluation of gene (polymorphic or monomorphic) function using knockout mutants. For the behavioural aspect, several parameters, including the type of aggression, measure of aggression, test situation and opponent type can have effects on the obtained genetics. This is illustrated for the offence type of attack behaviour in mice. The current combination of sophisticated genetic and behavioural analyses will result in time in the identification of many of the genes with effects on variation and development of one or more types of murine aggression. Since mouse and humans have many homologous genes mapped to homologous chromosome regions, it is conceivable that individual genes identified for one or more types of mouse aggression may be developed as animal models for human aggression. Genetic, physiological and behavioural limitations and uses of such models are discussed.
Aggression↗
Molecular genetic approaches to mammalian brain and behavior: an introduction.
Two of the goals of behavior genetics have been to identify individual genes with effects on brain and behavior and to determine the mechanism(s) for effects of individual genes on brain and behavior. With classical genetics, this would have consisted of identifying a gene by mapping it to a chromosome and of determining the pathways for its effects, tracing back from behavior or brain to the gene. Molecular genetics brings other approaches to these issues. Findings with molecular methods also lead to hypotheses with regard to mechanisms for effects of individual genes on brain or behavior. In this issue examples of molecular genetic approaches are described for perceptual (color vision and olfaction), motivational (circadian rhythms and sexual behaviors), learning and memory, and pathological (alcohol-related and schizophrenia) aspects of mammalian behavior.
Animals↗
Searching for candidate genes with effects on an agonistic behavior, offense, in mice.
It is well established that the agonistic behavior of offense in mice is heritable. However, few genes have been identified or mapped for offense. For segments of chromosomes with effects on offense, a positional candidate strategy can be used to find such genes. This approach is illustrated for the effect of the male specific part (nonpseudoautosomal region; NPAR) of the mouse Y chromosome on offense. It is proposed that a positional candidate for this effect is Sry. The Sry protein is a transcription factor. Its mRNA is expressed in fetal and adult brain. Its protein binds to response elements in the 5' end of the aromatase and the Fra1 genes. Each of these genes has potential effects on several brain neurotransmitter systems involved in offense. The NPAR Y chromosomes of several pairs of inbred strains have differential effects on offense. This hypothesis would be tested by sequencing Sry for some of these pairs of strains.
Aggression↗
Intermale aggression tested in two procedures, using four inbred strains of mice and their reciprocal congenics: Y chromosomal implications.
Indications of a role for the nonpseudoautosomal region of the Y chromosome (YNPAR) in intermale attack behavior have been demonstrated by Maxson's group using C57BL/10 (B10) and DBA/1 (D1) inbred mouse strains and their reciprocal congenics. Carlier and Roubertoux' group, using CBA/H (H) and NZB/B1NJ (N) mice, did not find such a YNPAR effect. For the two research groups, however, not only were the parental strains different, but also the rearing conditions and testing methods. The divergent conclusions drawn may therefore have been due either to genetic variation or to environment-related variables. We carried out two experiments to investigate these alternatives. The N and H strains were raised and tested according to the experimental design used by Maxson's group (homogeneous set test) and the D1 and B10 strains were raised and tested according to the experimental design of Carlier and Roubertoux' group (standard opponent test). Considering all studies together, the YNPAR effect appeared in both sets of mice only when using the homogeneous set test. This raises the question of what environmentally related variables are involved in the YNPAR effect on intermale attack. One strong hypothesis is that the different types of opponents in each experimental design send differing olfactory signals, which, in turn, differentially affect the capacity to elicit intermale attack behavior.
Aggression↗
Transcription of the Y chromosomal gene, Sry, in adult mouse brain.
The Y chromosomal gene Sry encodes a putative transcription factor which appears to serve as a master switch initiating testicular development. Here we show that this gene is transcribed in hypothalamus, midbrain, and testis of adult male but not adult female mice. In contrast to its circular transcripts in adult testis, those in brain are linear and may be translated. We propose that Sry exerts a role in the regulation of sex differentiation of the mammalian nervous system.
Animals↗
Alleles of the microsomal steroid sulfatase gene (Sts) in the pseudoautosomal region of the heterosomes of the mouse.
The gene (Sts) for microsomal steroid sulfatase (STS-EC 3.1.6.2) is located at the distal end of the pseudoautosomal region of the mouse heterosomes. A new improved method was developed to measure the activity of this enzyme in four inbred strains of laboratory mice, their respective congenics for the non pseudoautosomal region of the Y chromosome and their F1s were employed. The method was shown to be highly reliable (.95). No sexual dimorphism was shown but a polymorphism for the enzymatic activity, corresponding to three functional allelic forms was found. The results presented here are compatible with the location of the Sts gene on the X-Y pseudoautosomal region. The underdominance that appears in the F1s, in one set of strains and the difference between reciprocal F1s in the other set must be interpreted cautiously since it is the enzymatic activity which is only measured and not the protein itself. A complex mechanism, involving the gene responsible for the enzyme located on the pseudoautosomal region and autosomal locus or loci which regulate(s) its activity, is suggested as being responsible for the results obtained with the F1s.
Alleles↗
Olfactory discrimination of urinary odortypes from congenic strains (DBA/1Bg and DBA1.C57BL10-YBg) of mice differing in their Y chromosomes.
Differential effects of one or more genes in the nonpseudoautosomal region of the DBA1 and C57BL10 Y chromosomes on offensive attack may be mediated, at least in part, by differential effects of this Y chromosomal gene(s) on the sending and receiving of discriminable urinary odortypes. This hypothesis is based, in part, on the report that urine from a pair of Y chromosomal congenic strains (C57BL6.AKR-Y and C57BL6) of mice can be discriminated in a Y maze test. The AKR and C57BL6 Y chromosomes come from two distinct species of mouse (Mus domesticus and Mus musculus, respectively). Thus, this Y chromosomal variant exists between mouse species. The DBA1 and C57BL10 Y chromosomes come from a single species, Mus musculus. Here we show that in the Y maze system previously used, urine from mice with the DBA1 and with the C57BL10 Y chromosomes can also be discriminated. Thus, there are discriminable urinary odortypes for this pair of Y chromosomes from the same species, Mus musculus.
Animals↗
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.
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.
Animals↗
The evolution of the mammalian Y chromosome.
There is a predominant theory for the evolution of the mammalian Y chromosome. This theory hypothesizes that genes for sex determination and male-specific traits, as well as sequences for X-Y meiotic pairing, are conserved on the mammalian Y chromosome across all lineages and that all other Y chromosomal genes or sequences have been or will be lost in each mammalian lineage. There are effects of mouse Y chromosomal genes on behaviors and other traits that are not male specific. Under the predominant theory, these Y chromosomal genes could be the same as the conserved genes for sex determination or male-specific traits, or they could be genes that have been lost from the Y chromosomes of other mammalian lineages and that will eventually be lost from the Y chromosome of the rodent lineage. Recently, the evolution of the primate and rodent Y chromosomes has been studied at the DNA level. These studies are summarized and reviewed in this article. The findings of these studies are not fully consistent with the predominant theory for the evolution of the mammalian Y chromosome. Also, they imply that there are other possibilities for the phylogenetic history of Y chromosomal genes of mice with effects on behavior. These are that Y chromosomal genes with effects on mouse behaviors or other traits could be conserved genes other than those for sex determination or male-specific traits or that they could be novel genes on the Y chromosome of the rodent or Mus lineage.
Animals↗
Differential effect of the DBA1 and C57BL10 Y chromosomes on the response to social or other stimuli for offense.
Offense was measured in a homogeneous set test and a standard opponent test for two congenic strains of mice. The two congenic strains were DBA1Bg and DBA1.C57BL10Y-Bg, which differ in the Y chromosome. DBA1 males were more aggressive than DBA.C57BL10-Y meles in the homogeneous set test, whereas DBA1.C57BL10-Y males were more aggressive than DBA1 males in the standard opponent test. These findings are consistent with the hypothesis that this Y-chromosomal variant affects an individual's response to social or other stimuli for offense rather than its display of social or other stimuli for offense or its fighting propensity per se. It may be that this is a differential response to urinary chemo-signals.
Aggression↗
Effects of the heterosomes and maternal environments on aggressive behavior in Mus musculus.
This is a study of the offense type of aggression in males of the DBA/1Bg and C57BL/10Bg inbred strains of mice and their two reciprocal F1 hybrids. It uses three test paradigms for dyadic encounters: the homogeneous set test, an identity panel of testers, and the standard opponent test. There were no reciprocal F1 hybrid differences for any of the 12 behavioral measures of aggression in the homogeneous set test or the standard opponent test. For the panel of testers paradigm, reciprocal F1 hybrid differences occurred when the tester (opponent) was an F1 hybrid male, but not when the tester (opponent) was an RB/1 or C57BL10 male. When B10RB1F1 males were the testers (opponents), B10RB1F1 hybrid males were more aggressive than RB1B10F1 hybrid males across 10 of the 12 behavioral measures. Conversely, when RB1B10F1 males were the testers (opponents), RB1B10F1 males were more aggressive than B10RB1F1 males across 9 of the 12 behavioral measures. These results conform to the following empirical rule: A significant difference between reciprocal F1 hybrids is observed for these behavioral measures when one of the hybrids has both of its heterosomes (X and Y chromosomes) and its maternal environment identical to those of its opponent and the other hybrid has none of these identical to those of its opponent. These results are consistent with a model in which on some genetic backgrounds, but not on others, similarity of the heterosomes and maternal environments can influence the display of or response to social or other stimuli for the offense type of aggression in mice. These stimuli may be individual recognition chemosignals in urine.
Aggression↗
The Y chromosome, social signals, and offense in mice.
Offense is one type of aggression in mice (Mus musculus/Mus domesticus). Offense was measured in a panel of testers design for two congenic strains of mice. The two congenic strains were DBA1Bg and DBA1. C57BL10-YBg. These differ in the Y chromosome. Offense was measured for the following dyadic pairs: Group 1 (DBA1 tested against a DBA1 opponent); Group 2 (DBA1 tested against a DBA1.C57BL10-Y opponent); Group 3 (DBA1.C57BL10-Y tested against a DBA1.C57BL10-Y opponent); and Group 4 (DBA1.C57BL10-Y tested against a DBA1 opponent). Group 1 was more aggressive than Group 3, whereas Group 2 was no more aggressive than Group 4. Thus, when the experimental and opponent pairs have the same Y chromosome, the congenics differ in offense, whereas when the experimental and opponent pairs have different Y chromosomes, the congenics do not differ in offense. These findings are consistent with the hypothesis that these Y chromosomes affect the display of and response to social or other stimuli for offense of mice. These stimuli may be individual recognition chemosignals in urine.
Aggression↗