B6.Cg-Hbb^d3th Tg(LCR-HBA2,LCR-HBB)11Cos/HhbJ

Stock number: 031405
Product name: NY1DD
Strain synonyms: alpha^Hbeta^S; α^Hβ^S

Description

These NY1DD mice express human alpha-globin and human beta-S globin in red blood cells, carry the Hbb^d3th allele, and have applications in studies of thalassemia and sickle cell anemia.

Detailed description

These NY1DD mice carry the Hbb^d3th allele and the α^Hβ^S transgene, expressing human alpha-globin and human beta-S globin in red blood cells (RBC). Mice hemizygous or homozygous for the Tg(LCR-HBA2,LCR-HBB)11Cos transgene, on the FVB/N genetic background, express human beta-globin S in 36% of all RBC with a 1.35 ratio of human alpha to human beta chains. Mice heterozygous for the Hbb^d3th allele and hemizygous for the Tg(LCR-HBA2,LCR-HBB)11Cos transgene (on a mixed FVB, C57BL/6J, DBA/2J background) have 54% human beta-globin S chains, and an equal number of human alpha to human beta chains (ratio of 1). NY1DD, also called α^Hβ^S[β^MDD], mice, homozygous for the Hbb^d3th allele and hemizygous for the Tg(LCR-HBA2,LCR-HBB)11Cos transgene (on a mixed FVB, C57BL/6J, DBA/2J background), have 73% human beta-globin S chains and a human alpha to human beta chain ratio of 0.73, develop reticulocytosis after 30 days of age. NY1DD mice exhibit mean corpuscular hemoglobin concentration (MCHC) approximately 3 g/dL higher than that observed in wildtype controls and 39% of RBC sickle under under deoxygenated conditions. Southern blot analysis showed multiple copies of the co-injected transgene. Genotyping assays developed by The Jackson Laboratory were validated by HPLC analysis.

When crossed to the S Antilles strain (Stock No. 031710) the resulting mice exhibit a more severe sickling phenotype.

Development

Dr. Frank Costantini (Albert Einstein College of Medicine) designed a transgenic insert containing the human alpha globin 2 (HBA2) gene from the locus control region (LCR) of the human beta globin gene (HBB) and a second transgenic insert containing the human beta globin (HBB) gene from the locus control region of the human beta globin (HBB) gene. These constructs were co-injected into fertilized FVB/N mouse eggs. Southern blot analysis showed multiple copies of the co-injected transgene. The mice were backcrossed to C57BL/6J for approximately 10 generations. The transgenic mice were then crossed to B6.D2-Hbb^d3th/BrkJ (Stock No. 000996). 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(LCR-HBA2,LCR-HBB)11Cos
Name: transgene insertion 11, Frank Costantini
MGI accession ID: MGI:3794861
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: alpha^Hbeta^S; NY1DD; NY-S
Marker symbol: Tg(LCR-HBA2,LCR-HBB)11Cos
Marker name: transgene insertion 11, Frank Costantini
Marker synonyms: alpha^Hbeta^S; NY1DD; NY-S
Chromosome: UN
Strain of origin: FVB/N
Molecular note: Constructs expressing the human alpha globin 2 gene from the locus control region of the human beta globin gene and the human beta globin gene also from the human locus control region were coinjected to create a line of mice with cointegrated transgenes. Transgene expression is noted in red blood cells.

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.