This work proves the pathogenicity of four substitution mutations in the androgen-binding domain of the human androgen receptor (hAR) gene of four subjects with varying degrees of androgen insensitivity syndrome (AIS): complete (CAIS), partial (PAIS), or mild (MAIS). Of three unrelated CAIS subjects, two have Arg830Leu, the third has Arg830Gln. Their genital skin fibroblasts (GSF) have negligible androgen binding, but in overexpressing transfectants, the mutant androgen-binding activities have increased dissociation rates and decreased affinity for androgen. Owing to the instability of AR-androgen complexes, both mutants fail to transactivate a reporter gene. Glu771Ala and Arg870Gly caused PAIS and MAIS, respectively. Their normal levels of GSF androgen-binding activity have normal androgen affinity but increased dissociation rates. In transfectants, rates of dissociation resemble those in GSF, but the androgen affinities are questionably abnormal. Instability of Glu771Ala and Arg870Gly AR-androgen complexes caused subnormal transactivation of a reporter gene.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.23299 |
| Date | January 1995 |
| Creators | Shkolny, Dana |
| Contributors | Pinsky, Leonard (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001475221, proquestno: MM08053, Theses scanned by UMI/ProQuest. |
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