Chromosome 11p15.5 harbors a gene or genes involved in Beckwith Wiedemann Syndrome (BWS) and that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. PowerBLAST of P1 artificial chromosome clones from this region identified two novel transcripts with open reading frames encoding putative proteins of 253 and 424 amino acids. The larger of the transcripts was shown by Northern blot to be predominantly expressed in the fetal and adult liver and kidney. This transcript shares homology with integral membrane organic cation transporters, such as the tetracycline resistance proteins and bacterial multidrug resistance proteins; and was therefore designated ORCTL2 (organic cation transporter-like 2). An expressed sequence polymorphism provided evidence that the ORCTL2 gene exhibits "leaky" imprinting in both human fetal kidney and human fetal liver. Given the expression pattern of ORCTL2, it is possible that this gene may have a role in the development of phenotypes associated with BWS, including Wilms' tumor (WT). SSCP analysis on 51 sporatic WT samples did not identify any mutations in ORCTL2 which would implicate it in disease. Investigation of the transport properties of ORCTL2 show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry performed with anti-ORCTL2 polyclonal antibodies on human renal sections indicate that ORCTL2 is localized on the apical membrane surface of the proximal tubules. These results suggest that ORCTL2 may play a role in the transport of chloroquine and quinidine related compounds within the kidney.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20973 |
| Date | January 1998 |
| Creators | Reece, Mark T. |
| Contributors | Pelletier, Jerry (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 Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650438, proquestno: MQ50864, Theses scanned by UMI/ProQuest. |
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