B6.D2-Hbb^d3th/BrkJ

Stock number: 000996
Product name: beta-thalassemia
Research areas: Hematological Research

Description

These mice carry a spontaneous deletion at the Hbb locus characterized by hypochromic, microcytic anemia with severe anisocytosis, poikilocytosis, and reticulocytosis.

Detailed description

Homozygous Hbb^d3th mice survive to adulthood and reproduce but are smaller at birth than their littermates and demonstrate a hypochromic, microcytic anemia with severe anisocytosis, poikilocytosis, and reticulocytosis and the presence of inclusion bodies in a high proportion of circulating erythrocytes. Mice heterozygous for the deficiency demonstrate a mild reticulocytosis but are not clinically anemic. Analysis of globin chain synthesis in vitro by 3H-leucine incorporation reveals that beta-globin synthesis is nearly normal (95%) in heterozygotes and about 75% of normal in deficiency homozygotes. Molecular characterization of the mutation by restriction analysis reveals a deletion of about 3.3 kb of DNA, including regulatory sequences and all coding blocks for beta-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele represent the first animal model of beta-thalassemia (Cooley's anemia), a severe genetic disease of humans.

Development

The Hbb^d3th mutation was first identified in the progeny of a C57BL/6J female and an ethylnitrosurea treated DBA/2J male, but it was subsequently shown that the DBA/2J male had the mutation so it was not chemically induced. In 1984 homozygous males were sent from Dr. Susan Lewis to Dr. Jane Barker at The Jackson Laboratory and this mutation was backcrossed onto C57BL/6J. In 1995 embryos were generated for cryopreservation from C57BL/6J females bred to heterozygous males at backcross generation N24.

Allele

Symbol: Hbb^d3th
Name: beta-thalassemia
MGI accession ID: MGI:1856047
Generation method: Spontaneous
Synonyms: beta^major; beta^MDD; Hbb^d3(th); Hbb^th1; Hbb^th-1; Hbb^UNC
Marker symbol: Hbb
Marker name: hemoglobin beta chain complex
Chromosome: 7
Strain of origin: DBA/2J
Molecular note: A 3.7 kb region, including the entire beta major globin gene and 2 kilobases of 5' flanking region, is deleted. A novel approximately 66 bp sequence ending in a poly(A) stretch was found to bridge the deletion.