Identification of quantitative trait loci that affect aggressive behavior in mice

被引:68
作者
Brodkin, ES [1 ]
Goforth, SA [1 ]
Keene, AH [1 ]
Fossella, JA [1 ]
Silver, LM [1 ]
机构
[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
关键词
aggression; quantitative trait locus; QTL; individual differences; genetics; complex trait analysis; inbred mouse strain; NZB/B1NJ; A/J; behavior;
D O I
10.1523/JNEUROSCI.22-03-01165.2002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Despite the previous development of single-gene knock-out mice that exhibit alterations in aggressive behavior, very little progress has been made toward identifying the natural gene variants (alleles) that contribute to individual or strain differences in aggression. Whereas most inbred mouse strains show an intermediate level of inter-male aggression in the resident-intruder or dangler behavioral tests, NZB/B1NJ mice are extremely aggressive and A/J mice are extremely unaggressive. We took advantage of the large phenotypic difference between these strains and used an outcross-backcross breeding protocol and a genome-wide scan to identify aggression quantitative trait loci (QTLs) on distal chromosome 10 (Aggr1; p = 6 x 10(-7)) and proximal chromosome X (Aggr2; p = 2.14 x 10(-5)). Candidate genes for Aggr1 and Aggr2, respectively, include the diacylglycerol kinase alpha subunit gene (Dagk1) and the glutamate receptor subunit AMPA3 gene (Gria3). This is the first report of significant aggression QTLs established through a genome-wide scan in any mammal. The mapping of these QTLs is a step toward the definitive identification of mouse alleles that affect aggression and may lead, ultimately, to the discovery of homologous alleles that affect individual differences in aggression within other mammalian species.
引用
收藏
页码:1165 / 1170
页数:6
相关论文
共 40 条
[1]   Olfactory receptors, vomeronasal receptors, and the organization of olfactory information [J].
Bargmann, CI .
CELL, 1997, 90 (04) :585-587
[2]   ABNORMAL-BEHAVIOR ASSOCIATED WITH A POINT MUTATION IN THE STRUCTURAL GENE FOR MONOAMINE OXIDASE-A [J].
BRUNNER, HG ;
NELEN, M ;
BREAKEFIELD, XO ;
ROPERS, HH ;
VANOOST, BA .
SCIENCE, 1993, 262 (5133) :578-580
[3]  
CADORET RJ, 1995, ARCH GEN PSYCHIAT, V52, P916
[4]   AGGRESSIVE-BEHAVIOR AND ALTERED AMOUNTS OF BRAIN-SEROTONIN AND NOREPINEPHRINE IN MICE LACKING MAOA [J].
CASES, O ;
SEIF, I ;
GRIMSBY, J ;
GASPAR, P ;
CHEN, K ;
POURNIN, S ;
MULLER, U ;
AGUET, M ;
BABINET, C ;
SHIH, JC ;
DEMAEYER, E .
SCIENCE, 1995, 268 (5218) :1763-1766
[5]   HERITABILITY OF IRRITABLE IMPULSIVENESS - A STUDY OF TWINS REARED TOGETHER AND APART [J].
COCCARO, EF ;
BERGEMAN, CS ;
MCCLEARN, GE .
PSYCHIATRY RESEARCH, 1993, 48 (03) :229-242
[6]   Heritability of aggression and irritability: A twin study of the Buss-Durkee aggression scales in adult male subjects [J].
Coccaro, EF ;
Bergeman, CS ;
Kavoussi, RJ ;
Seroczynski, AD .
BIOLOGICAL PSYCHIATRY, 1997, 41 (03) :273-284
[7]   Sex differences in the etiology of aggressive and nonaggressive antisocial behavior: Results from two twin studies [J].
Eley, TC ;
Lichtenstein, P ;
Stevenson, J .
CHILD DEVELOPMENT, 1999, 70 (01) :155-168
[8]   Presynaptic dopaminergic deficits in Lesch-Nyhan disease [J].
Ernst, M ;
Zametkin, AJ ;
Matochik, JA ;
Pascualvaca, D ;
Jons, PH ;
Hardy, K ;
Hankerson, JG ;
Doudet, DJ ;
Cohen, RM .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (24) :1568-1572
[9]  
Ferris CF, 1997, J NEUROSCI, V17, P4331
[10]   INTERMALE AGGRESSION TESTED IN 2 PROCEDURES, USING 4 INBRED STRAINS OF MICE AND THEIR RECIPROCAL CONGENICS - Y-CHROMOSOMAL IMPLICATIONS [J].
GUILLOT, PV ;
CARLIER, M ;
MAXSON, SC ;
ROUBERTOUX, PL .
BEHAVIOR GENETICS, 1995, 25 (04) :357-360