title: Lethal alpha-thalassaemia created by gene targeting in mice and its genetic rescue.
abstract: Mutations at the alpha-globin locus are the most common class of mutations in humans, with deletion of all four adult alpha-globin genes resulting in the perinatal lethal condition haemoglobin Barts hydrops fetalis. Using gene targeting in mice, we have deleted a 16 kilobase region encompassing both adult alpha-globin genes. Animals homozygous for this deletion become hydropic and die late in gestation mimicking humans with hydrops fetalis. Introduction of a human alpha-globin transgene rescued these animals from perinatal death thus demonstrating the utility of this murine model in the development of cellular and gene based approaches for treating this human genetic disease.
authors.affiliation: Human Genome Center, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
authors.forename: C
authors.initials: C
authors.lastname: Pászty
authors.forename: N
authors.initials: N
authors.lastname: Mohandas
authors.forename: M E
authors.initials: ME
authors.lastname: Stevens
authors.forename: J F
authors.initials: JF
authors.lastname: Loring
authors.forename: S A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: C M
authors.initials: CM
authors.lastname: Brion
authors.forename: E M
authors.initials: EM
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002678:Chimera; D004195:Disease Models, Animal; D005313:Fetal Death / Q000209:etiology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D015316:Genetic Therapy; D005865:Gestational Age; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006455:Hemoglobins, Abnormal; D006801:Humans; D015160:Hydrops Fetalis / Q000097:blood / Q000196:embryology / Q000235:genetics* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics*; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics / Q000628:therapy
chemical_list: D006455:Hemoglobins, Abnormal; D005914:Globins; C030448:hemoglobin Bart's