B6.Cg-Hbb^d3th Tg(HBB-AR-HBA2,-HBB*)58Rub/J

Stock number: 031710
Product name: S Antilles
Research areas: Hematological Research, Research Tools

Description

These S Antilles mice express human HBA2 (hemoglobin subunit alpha 2) gene and mutant Sickle Antilles human HBB gene in red blood cells, carry the Hbb^d3th allele, and have applications in studies of hemoglobinopathy, thalassemia and sickle cell anemia.

Detailed description

These S Antilles mice carry the Hbb^d3th allele and the α beta;^{S Antilles} transgene, which contains the human HBA2 (hemoglobin subunit alpha 2) gene and mutant Sickle Antilles human HBB gene in red blood cells (RBC). Mice that are homozygous for the Hbb^d3th allele and hemizygous for the Tg(HBB-AR-HBA2,-HBB*)58Rub transgene, exhibit reticulocytosis and under deoxygenating conditions 30% of red blood cells exhibit sickling. Mice that are homozygous for the transgene are viable and fertile. Genotyping assays developed by The Jackson Laboratory were validated by HPLC analysis.

Development

The Tg(HBB-AR-HBA2,-HBB*)58Rub transgenes, designed by Dr. Edward M. Rubin (Lawrence Berkeley Laboratory, University of California), consisting of an 800 bp DNA fragment containing the hypersensitive II (HSII) region of the human HBB (hemoglobin subunit beta) locus control region upstream of the human HBA2 (hemoglobin subunit alpha 2) gene and mutant human HBB gene containing the Sickle Antilles mutations (G6V and V23I), were co-injected into the male pronuclei of Swiss Webster fertilized eggs. Founder line 58 mice have approximately 4 copies of HBA2 and 10 copies of the mutant HBB. The mice were then crossed to mice carrying the Hbb^d3th, on the C57BL/6J genetic background. The mice were then backcrossed to C57BL/6J for more than 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(HBB-AR-HBA2,-HBB*)58Rub
Name: transgene insertion 58, Edward M Rubin
MGI accession ID: MGI:4411997
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: alphabeta^{S Antilles}
Marker symbol: Tg(HBB-AR-HBA2,-HBB*)58Rub
Marker name: transgene insertion 58, Edward M Rubin
Chromosome: UN
Strain of origin: Swiss Webster
Molecular note: The 800 bp DNA fragment containing the hypersensitive II region of the human HBB locus control region was used to drive erythroid-specific expression of human HBA2 and human HBB containing the Sickle Antilles mutations (G6V and V23I) in co-injected constructs. Two founders were generated (14 and 58). The line from founder 58 contains 4 copies of the HBA2 expressing construct and 10 copies of the HBB* expressing construct.

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.