STOCK Tg(LCR-HBG2,-HBG1)1352Hhb/J

Stock number: 031707
Product name: low gamma, low γ, LCR^Gγ^Aγψβ
Research areas: Hematological Research, Research Tools

Description

Low gamma transgenic mice carry the LCR^Gγ^Aγψβ transgene and may be suitable for use in studies related to sickle cell anemia and hemoglobinopathy.

Detailed description

These transgenic mice carry the low gamma, LCR^Gγ^Aγψβ, transgene. γ-globin gene expression (mRNA from red blood cells, as assessed by RNase protection assay) is 0.3% in adult animals, a 70-fold decrease from the 23% γ-globin mRNA level (per transgene copy) in 13.5-day embryos, indicating appropriate developmental silencing of the γ-globin transgene. In peripheral blood from adult transgenic mice no γ-globin chains are detected by HPLC. The originating investigator reports there are 2 copies of the transgene. Hemizygotes are viable and fertile. Homozygous viability/fertility has not been tested (February 2018). The Donating Investigator suggests extending weaning for smaller pups.

Development

The approximately 32 kb low gamma, LCR^Gγ^Aγψβ, transgene, designed by Dr. Bernard G. Forget (Yale University School of Medicine), containing the human beta-globin gene LCR cassette, the human Gγ-globin and Aγ-globin genes, and 14 kb of downstream sequences including the ψβ pseudogene and ending 5' to the δ-globin gene, was injected into the pronuclei of (C57BL/6 x SJL)F2 zygotes. Founder line 1352 was subsequently established. The low gamma transgenic mice were then bred to the Berkeley model mice on a congenic C57BL/6J background: B6.Cg-Hba^tm1Paz Hbb^tm1Tow Tg(HBA-HBBs)41Paz. 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), and bred to remove the Hba^tm1Paz Hbb^tm1Tow alleles and Tg(HBA-HBBs)41Paz transgene.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. The results suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6 and SJL genetic background.

Allele

Symbol: Tg(LCR-HBG2,-HBG1)1352Hhb
Name: transgene insertion 1352, Henny Billett
MGI accession ID: MGI:6277094
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: LCR ^Ggamma ^Agamma psi beta
Marker symbol: Tg(LCR-HBG2,-HBG1)1352Hhb
Marker name: transgene insertion 1352, Henny Billett
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Molecular note: The human beta globin cluster is modified such that the locus control region (LCR) consisting of 4 DNAse I hypersensitive site (HS4-1) is inserted upstream of HBG2, HBG1, and the HBBP1 pseudogene. Founder line 1352 was established. Expression of the HBG2 gene is 3-7 fold higher than the HBG1 gene in embryonic and fetal erythroid cells.