Genetic mapping of the rat agu gene

• Main Author: Duran Alonso, Maria Beatriz
• Published: University of Glasgow 1997
• Subjects: 572.8; QH426 Genetics
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340749

In 1993, a mutant strain, AS/AGU arose spontaneously in an enclosed colony of the Albino Swiss (AS) strain of rat. AS/AGU animals exhibit a set of locomotor abnormalities. They display a general instability and whole body tremor, are slow at initiating movement, show reductions in purposeful action, and perform poorly at locomotor tests such as mid-air righting. L-dopa administration or fetal midbrain transplants reverse the majority of the symptoms, resembling the observations made on Parkinson's disease patients. These features make the AS/AGU strain a useful model for movement disorders due in significant part to failure of the dopaminergic transmission system. Crosses of AS/AGU to other laboratory rat strains point to a single recessive mutation with essentially complete penetrance (agu/agu) as the cause of the abnormal phenotype. There is no evidence of sex linkage or maternal inheritance. In the absence of any evidence of the function of the agu gene product, positional cloning of this locus was begun. The first step was the establishment of a genetic map location for the agu locus. A large series of microsatellite markers were analysed and used to identify which of the strains PVG, BN, and F344 differed to a greater extent from AS/AGU. Differences at 43%, 62% and 47% of the loci were recorded, respectively. BN and F344 were therefore selected as the reference strains in backcrosses to AS/AGU, in an attempt to maximise the number of informative markers which could be used to type the progeny.