German Journal of Psychiatry ISSN 1455-1033
2000, Vol. 3, Supplement 1, S10
Knockout-mice and humans with panic disorder
of Psychiatry, University of Münster, Albert-Schweitzer-Str.11, D-48149 Münster,
Panic disorder is a common anxiety disorder with a complex genetic background. The method of choice to delineate the relevant genetic factors are association studies by means of which genes with minor effects can be detected. Candidate genes in general have been chosen on the basis of the molecular mechanisms of therapeutic agents or panic–provoking agents (e.g. MAOAI1, caffeine). The detection of genes involved in unknown pathophysiological pathways thus is not possible. Knockout-mice are mice which lack one or several defined genes. They allow to develop hypotheses for which human disease phenotype the knocked- out gene may be relevant. In particular, there are several well characterized behavioral paradigms for the rodent equivalents of avoidant behavior (elevated plus or zero maze) and anticipation anxiety (prepulse inhibition of startle) which can be studied in knockout mice. This approach has already provided the first unsuspected candidate genes (e.g. CREM2, reelin). The now possible discovery of novel pathophysiological pathways will be the basis for the development of innovative therapeutic agents in the future.
1Deckert J et al., Hum Mol Gen
8:621-624, 1999; 2Maldonado R et al., PNAS USA 96: 14094-14099, 1999