B6;129-Bax^tm2Sjk Bak1^tm1Thsn/J

Stock number: 006329
Product name: Bax^fl Bak-
Research areas: Apoptosis Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These double mutant mice possess loxP sites flanking exons 2-4 of the Bax gene and a null allele of the Bak1 gene. This strain may be useful for generating conditional mutations in applications related to studies of B cell homeostasis.

Detailed description

Mice homozygous for both alleles (Bax^fl and bak-) are viable and fertile with no reported abnormalities. Splenic and thymic tissues display no Bak1 protein expression.

When bred to Cre recombinase expressing mice, the resulting offspring will have exons 2-4 of Bax deleted in the cre-expressing tissues (determined by promoter driving cre expression). The conditional deletion of Bax combined with the Bak1 null allele makes these mice useful in studies of apoptosis regulation, tissue homeostasis, and development in multiple cell lineages.

When bred to a strain with a Bak1 targeted null allele (Stock No. 004183) and to either a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 004126) or to a strain expressing interferon inducible Cre recombinase (Stock No. 003556), this mutant mouse strain may be useful in studies of autoimmune disease.

Development

These mutant mice have targeted mutations of Bax and Bak1. For targeted mutation of Bax, Dr. Stanley J. Korsmeyer's lab (Harvard Medical School) designed a vector to flank exons 2-4 with loxP sites. This construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Mice resulting from germline transmission of this Bax^fl allele (on a mixed B6;129 genetic background) were generated. For targeted mutation of Bak1, Dr. Craig B. Thompson's lab (University of Pennsylvania) designed a vector to replace exons 3-6 (encoding the Bcl2 homology domains) with a neo cassette. This construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 ES cells. Mice resulting from germline transmission of this allele (on a mixed B6;129 genetic background) were generated. These two mutant strains were bred together and maintained as homozygotes by Dr. Stanley J. Korsmeyer's lab (Harvard Medical School) prior to arrival at The Jackson Laboratory.

Allele

Symbol: Bak1^tm1Thsn
Name: targeted mutation 1, Craig B Thompson
MGI accession ID: MGI:2159364
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Bak1
Marker name: BCL2-antagonist/killer 1
Chromosome: 17
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neomycin resistance cassette replaced a genomic fragment containing exons 2-6. These exons encode the Bcl-2 homology domains of the encoded protein. Western blot analysis on spleen and thymus lysates derived from homozygous mice confirmed that no detectable protein is expressed from this allele.

Allele

Symbol: Bax^tm2Sjk
Name: targeted mutation 2, Stanley J Korsmeyer
MGI accession ID: MGI:3589203
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Bax
Marker name: BCL2-associated X protein
Chromosome: 7
Strain of origin: 129X1/SvJ
Molecular note: LoxP sites were inserted to flank exons 2-4. A loxP-flanked neo was removed via cre-mediated recombination.