The mouse multidrug resistance mdr gene family is composed of three closely related members termed mdr1, mdr2, and mdr3. Gene specific hybridization probes have been used to determine that the three mdr genes are linked on a chromosomal segment of 625 kilobases, with the gene order and orientation: (5$ sp prime$) mdr3 (3$ sp prime$)-(5$ sp prime$) mdr1 (3$ sp prime$)-(3$ sp prime$) mdr2 (5$ sp prime$). In independently derived cell lines, we observed that the emergence of multidrug resistance is linked to the overexpression of either and mdr1 or the mdr3 gene. The mdr1 gene has been isolated and its genomic organization determined: the gene spans 68 kilobases, is split into 28 exons encoding discrete predicted domains of the protein, and appears to originate from the duplication of an intron-containing ancestor gene. The mdr1 promoter has been cloned, sequenced, and the transcription start site localized. The transcriptional activities of 5$ sp prime$ deletion fragments from the mdr1 promoter fused to a reporter gene have been tested by transient transfection in a panel of mouse cell lines. These studies have allowed the identification of proximal and distal regions in the mdr1 promoter, containing basal and cell-specific transcriptional activities.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74614 |
| Date | January 1990 |
| Creators | Raymond, Martine |
| 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 | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001215379, proquestno: AAINN67640, Theses scanned by UMI/ProQuest. |
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