TY - JOUR
T1 - Mapping quantitative trait loci for fear-like behaviors in mice
AU - Gershenfeld, Howard K.
AU - Paul, Steven M.
N1 - Funding Information:
H.G. thanks C. B. Taylor, I. L. Weissman, and D. Baltimore for encouragement in the larval stages of this project. We appreciate helpful conversations with C. Mathis, J. Crawley, P. Neumann, E. Remmers, J. Thomas, E. Ginns, R. Philibert, W. Dietrich, E. Lander, C. Basten, Z. B. Zeng, and our NIH and UTSW colleagues. We sincerely thank Xiaohua Li, C. Shaver, D. Brown, and M. deBlaquiere for superb technical assistance. We are grateful to the NIMH Com- puter support group, the Whitehead/MIT Mouse Genome Project, Research Genetics, and the Mouse Genome Informatics Project for providing the infrastructure for this work. This project has been generously supported by NIMH-IRP, a NARSAD Young Investigators Award (H.G.), the Southwestern Medical Foundation (H.G.), and the KZA Hope Fund (H.G.).
PY - 1997/11/15
Y1 - 1997/11/15
N2 - Two mouse models developed for screening anxiolytic drugs were selected for genetic analysis, namely 'wall-seeking' tendency in an open field ('thigmotaxis') and the light-to-dark transition (LD) paradigm, a conflict test. These tests measure differences in naturalistic tendencies of mice to explore a novel environment and to avoid a bright light or the center of an open field. In an F2 intercross of two strains of mice (A/J and C57BL/6J) that differ markedly in these behaviors, we estimated a broad sense heritability ranging from 0.3 to 0.59. With this intercross (n = 518), we have mapped several quantitative trait loci (QTL) for these behaviors by performing a genome-wide search. A significant QTL on chromosome 10 (near D10Mit237; LOD of 9.3) that affects LD behavior was identified, and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6, 15, 19, and X. For center time behaviors, QTL were identified on chromosome 1 (LOD of 7.7 and 4.0 for the initial 5-min epoch and the first trial average of the next two 5-min epochs, respectively), and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6 and 14. These QTL individually explain from 2.3 to 8.4% of the phenotypic variance. Collectively, the multiple independent QTL explain from 3.5 to 26.5% of the F2 population's phenotypic variance, depending on the trait. The complexity and heterogeneity of the genetic factors underlying these fear-like behaviors are illustrated by the lack of shared QTL between paradigms and by mapping different QTL for repeated trials of behavior. The identification of QTL affecting individual differences in fear-like behavior may lead to the identification of new gene products and pathways that modulate behavior, providing targets for rational drug design.
AB - Two mouse models developed for screening anxiolytic drugs were selected for genetic analysis, namely 'wall-seeking' tendency in an open field ('thigmotaxis') and the light-to-dark transition (LD) paradigm, a conflict test. These tests measure differences in naturalistic tendencies of mice to explore a novel environment and to avoid a bright light or the center of an open field. In an F2 intercross of two strains of mice (A/J and C57BL/6J) that differ markedly in these behaviors, we estimated a broad sense heritability ranging from 0.3 to 0.59. With this intercross (n = 518), we have mapped several quantitative trait loci (QTL) for these behaviors by performing a genome-wide search. A significant QTL on chromosome 10 (near D10Mit237; LOD of 9.3) that affects LD behavior was identified, and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6, 15, 19, and X. For center time behaviors, QTL were identified on chromosome 1 (LOD of 7.7 and 4.0 for the initial 5-min epoch and the first trial average of the next two 5-min epochs, respectively), and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6 and 14. These QTL individually explain from 2.3 to 8.4% of the phenotypic variance. Collectively, the multiple independent QTL explain from 3.5 to 26.5% of the F2 population's phenotypic variance, depending on the trait. The complexity and heterogeneity of the genetic factors underlying these fear-like behaviors are illustrated by the lack of shared QTL between paradigms and by mapping different QTL for repeated trials of behavior. The identification of QTL affecting individual differences in fear-like behavior may lead to the identification of new gene products and pathways that modulate behavior, providing targets for rational drug design.
KW - Anxiety
KW - Chromosomal mapping
KW - Fear
KW - Habituation
KW - Individual differences
KW - Quantitative trait loci (QTL)
UR - http://www.scopus.com/inward/record.url?scp=0031573448&partnerID=8YFLogxK
U2 - 10.1006/geno.1997.5002
DO - 10.1006/geno.1997.5002
M3 - Article
C2 - 9403052
AN - SCOPUS:0031573448
SN - 0888-7543
VL - 46
SP - 1
EP - 8
JO - Genomics
JF - Genomics
IS - 1
ER -