This investigation focuses on gyrate atrophy of the retina and choroid. This is one of the few types of retinitis pigmentosa in which the primary biochemical defect is known. Determination of the human chromosome which contains the gene for ornithine aminotransferase, the deficient enzyme in this disease: and, thus, the gene for gyrate atrophy of the retina and choroid, will be performed in somatic cell hybrids which contain mouse chromosomes and human chromosomes. Starch gel electrophoresis will be used to detect human and mouse ornithine aminotransferase. The human chromosome which is always present when human ornithine aminotransferase is present and always absent when human aminotransferase is absent will be the one containing the gene. Similar studies will be done to determine which specific portion of the human chromosome contains the gene. Mouse-hamster somatic cell hybrids will be used to determine the specific portion of mouse chromosome 7 containing the gene coding for ornithine aminotransferase. A mouse model of ornithine aminotransferase deficiency will be prepared by breeding mice with chromosome translocations. The pathophysiology of the disease and the response to treatment will be examined in this mouse model. The toxicity of ornithine in the rabbit retina will be examined. The distribution of ornithine aminotransferase in the rabbit retina will be determined with fluorescent antibody studies. Genetic complementation of the various mutations of ornithine aminotransferase in humans will be examined. The treatment response to vitamin B6 in a gyrate atrophy patient will be examined. Sophisticated noninvasive tests of retinal function will be used to define the specific parts of the retina affected by gyrate atrophy.
| O'Donnell, J J; Vannas-Sulonen, K; Shows, T B et al. (1988) Gyrate atrophy of the choroid and retina: assignment of the ornithine aminotransferase structural gene to human chromosome 10 and mouse chromosome 7. Am J Hum Genet 43:922-8 |
