Year: 2013
Type: dissertation
Abstract: The serotenergic and hypothalamic systems regulate mood and food intake, respectively, which can both be altered in neurodegenerative and psychiatric disorders. The spontaneous recessive anorexia (anx) mouse mutation has previously been shown to cause widespread deficits in serotonergic innervation, and more recently, hypothalamic neuronal degeneration. These neuronal deficits observed in anx/anx mice contribute to their emaciated appearance and abnormal behaviours. The anx mutation is located on mouse chromosome 2 in an interval syntenic to human 15q22, which has been linked with catatonic schizophrenia and cases of autism and phobic disorders. At present, while the mutation(s) causative of the anx phenotype remains unknown, I have further characterized a novel neurodegeneration phenotype in anx/anx brains. In addition, we have identified a genetic variant that contributes to the anx phenotype. To test the effects of the genetic variant, we generated normal and mutant transgenic mouse lines. The normal line resulted in the partial rescue of anx phenotypes. Conversely, the mutant line showed no rescue. Thus, we have identified the first genetic modifier of the anx phenotype. Given the neurobiological effects of the anx mutation coupled with its intriguing genetic location, further examining the anx mutation may contribute to a better understanding of human psychiatric and neurodegenerative disorders.
Source: TSpace (University of Toronto)
Author: Joanna Yu
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2751506472