To further our understanding of the complex pathophysiology of human sickle cell disease (SCD) and to develop better therapies, three transgenic mouse lines have been produced that survive on mostly human hemoglobin (Hb). These lines have been generated by crossing HbSAD (SAD) transgenic mice with other mice carrying a null deletion of the endogenous globin genes (alpha or beta), SAD/homozygous alpha-globin null (SADalpha -/-) mice display a SCD-like phenotype and have a dramatically reduced mean lifespan; therefore, this line provides a novel model for assessment of anti-sickling protocols or identifying epistatic modifiers genes. Intriguingly, SAD/heterozygous alpha-globin null (SADalpha+/-) mice have a mild phenotype compared to SAD mice. In stark contrast, the highest cellular HbSAD fraction and degree of in vivo sickling was obtained in SAD/compound heterozygous alpha- and beta-globin null (SADalpha +/-beta+/-) mice. These SADalpha +/-beta+/- mice display chronic anemia and delayed growth indicative of a severe phenotype, similar to the human HbSS phenotype.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.31559 |
| Date | January 2000 |
| Creators | Wright, Adrian C. |
| Contributors | Trudel, Marie (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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001803207, proquestno: MQ70528, Theses scanned by UMI/ProQuest. |
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