Characterization of a Novel Circling Mouse (Cr) Generated in a transgenic growth hormone mouse breeding colony

Abstract

Numerous genetic variants displaying stereotypic circling behaviour have been described in rodents. The majority are recessive mutants expressing dopaminergic alterations in the striatum- often with associated vestibular defects. We describe a novel circling mouse (Cr) with intact vestibular function frequently obtained from crosses of non-transgenic wild type mice (WT) and transgenic growth hormone mice (TGM). We have characterized Cr with stereotypic circling, head bobbing, hyperkinesia, aggressiveness, and elevated dopamine when compared to the transgenic growth hormone mouse. The Cr also demonstrates self-mutilating behaviour found in mice with dysregulated striatal dopamine levels. Cr oppositely mirrors most traits of the TGM including alterations in sleep, activity, eating, and drinking. TGM displayed superior performance than WT in novel object recognition, but this decreased with aging. Comparatively, Cr performed poorly in this test. The memory of young TGM exceeded controls, whereas young Cr displayed poorer memory with an age related improvement. In a stepdown test of emotionality, TGM step down more readily, while Cr are more hesitant than WT. TGM and Cr also demonstrate opposite alterations in striatal dopamine. Further analysis demonstrated differential responsiveness of TGM and Cr under dopaminergic drugs, and potentially sexually dimorphic differences in behaviour associated with elevated GH in TGM. TGM are characterized by increased levels of circulating growth hormone and alterations in sleep and activity. We hypothesize that frequent generation of Cr may reflect unintended selection of modifier genes that counterbalance negative consequences of elevated GH in TGM.