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. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22550 |
| Date | 03 1900 |
| Creators | Chaudhry, Alanna Mary |
| Contributors | Szechtman, Henry, Rollo, C. David, Biology |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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