Molecular Genetic Analysis of the Mouse Anorexia Mutation

• Main Author: Kim, Dennis
• Other Authors: Cordes, Sabine
• Language: en_ca
• Published: 2010
• Subjects: serotonin; mouse; 0369
• Online Access: http://hdl.handle.net/1807/32211

The serotonergic system regulates numerous behaviours and disruptions in this system have been associated with disorders of mood and mind. Although molecular genetic analysis has dissected many of the genes involved in the specification of the serotonergic system, relatively little is known about the mechanisms that promote axonal outgrowth from serotonin-producing neurons and how these projections are directed to innervate and form synapses with their appropriate targets. The mouse anorexia mutation causes hypersprouting of serotonergic projections in target fields and has provided us the unique opportunity to examine the crucial events that lead to the establishment of these complex serotonergic networks. Through positional cloning, I have identified a candidate gene that is upregulated during a time in which innervation and synaptogenesis of serotonergic neurons are maximal. I have assessed the expression of this candidate gene in the brain and have found striking differences in the pattern of expression between the normal and the mutant mouse. Furthermore, by using transgenic methods, I have partially rescued several hallmark behavioural phenotypes in the mutant mouse. Thus, this candidate almost certainly represents the “Anorexia” gene.