The human androgen receptor (hAR) is a ligand-activated, nuclear transcription factor. Mutations affecting the formation and/or action of the hAR cause androgen insensitivity syndrome (AIS). The majority of mutations identified to date are within the DNA- and hormone-binding domains; very few have been identified in the transactivational modulatory domain, encoded by exon 1. This work presents an analysis of exon 1 and the 5$ sp prime$-flanking region of the hAR in a set of subjects whose AIS was believed to be caused by a mutation within these regions. Six of twelve strains had a nonsense or frameshift mutation in exon 1; a seventh strain had two missense and one silent substitution; no mutations were identified in the remaining subjects. The two missense mutations were recreated, individually and together, in an hAR complementary DNA (cDNA) expression vector and expressed in heterologous COS-1 cells. Their pathogenicity could not be proven with the system and assays used. In addition, mRNA and protein levels were analyzed and correlated with the identified mutations and the subjects' phenotype.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27431 |
| Date | January 1996 |
| Creators | Vasiliou, Denise Marie. |
| Contributors | Pinsky, L. (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: 001555809, proquestno: MQ29806, Theses scanned by UMI/ProQuest. |
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