Phenotypic and genetic characterization of a short-term selective breeding for anxiety-related behavior

Closely leaned to the selective inbreeding protocol for anxiety-related behavior as applied for the generation of the high (HAB) and low (LAB) anxiety-related behavior mouse lines, we set up a short-term selective breeding (STSB) to select for behavioral extremes of anxiety as measured on the elevated plus-maze. Aim of the study was, to answer the question, if we were able to reproduce (i) the phenotypic comorbidities and (ii) some of the molecular underpinnings typical of the original breeding. Breeding has been conducted as to the 7th generation, resulting in the HAB-II and LAB-II mouse lines. The last generation of mice had been extensively tested in a behavioral test battery of diverse anxiety-related, locomotor and depression-like behavior tests. Subsequently, we also analyzed candidate genes from the HAB/LAB mouse model and related neurotransmitter systems in the STSB. Although all main phenotypic features of the HAB/LAB model could be reproduced in the STSB, which points to their strong mechanistic and genetic linkage to each other, only few candidate genes (Stx3 and Mt1) were also differentially regulated in the STSB. Additionally, we succeeded in reproducing alterations in the tachykinin, CRH and vasopressin/oxytocin systems that also exist in the original model. Thus, all key phenotypic features and some major molecular systemic differences seem to be closely linked and emphasize a strong involvement in producing the anxiety-related and depression-like phenotypes.