title: Towards a mouse model for sickle cell disease: HB SAD.
abstract: Very recently a high expression of human hemoglobin S, which causes sickle cell disease, has been obtained in transgenic mice. We have constructed a modified beta S gene, beta SAD which carries two additional mutations in order to induce polymerization of transgenic hemoglobin when diluted by endogenous mouse Hb. The transgenic SAD mice are not anemic but exhibit a low percentage of irreversible sickle cells. Sickling is induced by deoxygenation of erythrocytes in vitro. In addition, the anemia of neonates and the low incidence of SAD animals in the progeny suggest a deleterious effect of SAD Hb during development. Finally, hypoxia induces a high mortality in SAD adults suggesting the induction of vaso-occlusive events.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY 10032.
authors.forename: M
authors.initials: M
authors.lastname: Trudel
authors.forename: M C
authors.initials: MC
authors.lastname: Garel
authors.forename: N
authors.initials: N
authors.lastname: Saadane
authors.forename: P
authors.initials: P
authors.lastname: Rouyer-Fessard
authors.forename: D
authors.initials: D
authors.lastname: Vidaud
authors.forename: F
authors.initials: F
authors.lastname: Costantini
authors.forename: Y
authors.initials: Y
authors.lastname: Beuzard
mesh_terms: D000755:Anemia, Sickle Cell; D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D004195:Disease Models, Animal; D005914:Globins / Q000235:genetics; D006451:Hemoglobin, Sickle / Q000235:genetics*; D000860:Hypoxia / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic / Q000097:blood* / Q000235:genetics; D015202:Protein Engineering; D011994:Recombinant Proteins; D013923:Thromboembolism / Q000209:etiology
chemical_list: D006451:Hemoglobin, Sickle; D011994:Recombinant Proteins; C070168:hemoglobin SAD; D005914:Globins