International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 173 - MODELLING ANXIETY IN HETEROGENEOUS STOCK (HS) MICE: A NEW APPROACH FOR ASSESSING COMPLEX TRAIT IN AN OUTBRED MOUSE POPULATION

Liu L
SGDP Centre, Institute of Psychiatry, King's College London

Co-Authors: Fernandes C, Rijsdijk F, Paya-Cano JL, Plomin R, Schalkwyk LC
Institutions: SGDP Centre, Institute of Psychiatry, King's College London

Anxiety is a complex trait with a genetic contribution likely to be equally complex. Among a variety of anxiety tests that are currently used in behavioural genetic research, it is unclear the extent to which a common underlying phenotype of anxiety can be extracted from multiple tests or whether each test simply measures distinct situation-specific anxiety.

We have developed a mouse anxiety test battery (including open field, elevated plus maze, light/dark box and SHIRPA primary screen) to assess the structure of anxiety behaviours in order to facilitate genetic studies. Heterogeneous stock (HS) mice derived from outbred crosses from eight inbred strains were assessed. Model fitting techniques were applied to data obtained from 354 mice (177 full sib pairs) to select the best-fit phenotypic and genetic models. The best-fit genetic models based on the full sibling data show different genetic and environmental structures, which could explain why conventional factor analysis approaches and phenotypic models failed to detect a single factor structure from the phenotypic data. Multivariate genetic analyses on this model showed heritability estimate of 40% for anxiety measures regressed by related maze activity. Both general additive genetic factor for latent anxiety and multiple maze-specific factors were identified in a hierarchical structure, although in this model genetic influence seems largely test-specific rather than general across most activity regressed anxiety measures. In contrast, maze activity measures yielded a general genetic factor across the tests. Our findings provide new insight into the mouse anxiety models that are widely used in behavioural genetic research.


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