The mouse homologue of the human tuberous sclerosis 2 (TSC2) gene maps to chromosome 17, but does not fall within the t{sup w18} or t{sup h20} deletions
- Univ. College London (United Kingdom)
- MRC Radiobiology Unit, Oxon (United Kingdom); and others
Tuberous sclerosis, TSC, is an autosomal dominant disorder characterized by a variety of clinical features including mental retardation, epilepsy, facial angiofibroma, shagreen patches on the skin, rhabdomyomas of the myocardium, and renal cysts. Genetic heterogeneity of the disorder has been established, with two distinct genetic loci mapping to 9q34 (TSCI; 4) and 16p13.3 (TSC2; 8). The locus on 16p13 is thought to account for about 60% of cases of TSC. This locus was recently cloned. Five TSC-associated deletions were found using pulsed-field gel electrophoresis (PFGE), covering a region of 120 kb. This region was cloned, and four genes were isolated. One of these had a region of homology to the GTPase-activating protein GAP3, was widely expressed, fell within each of the five deletions identified by PFGE, and displayed intragenic deletions in five more TSC patients, including one de novo deletion. This gene was designated TSC2. Tuberous sclerosis appears, therefore, in 60% of cases, to result from a loss of function of a single allele at the TSC2 locus. This suggests that it might be possible to generate a mouse model for TSC by knocking out a single allele at the homologous mouse locus. Since there are defined deletions corresponding to many regions of the mouse genome (either spontaneous or induced by radiation or chemical mutagenesis), we set out to map the mouse homologue of TSC2 to determine whether deletions of Tsc2 might already in fact exist. 12 refs., 1 fig.
- OSTI ID:
- 219911
- Journal Information:
- Genomics, Journal Name: Genomics Journal Issue: 2 Vol. 26; ISSN GNMCEP; ISSN 0888-7543
- Country of Publication:
- United States
- Language:
- English
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