B6;129-Mcl1^tm3Sjk/J

Stock number: 006088
Product name: Mcl-1^{f
Research areas: Apoptosis Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research, Research Tools}

Description

These floxed mutant mice possess loxP sites flanking exon 1 of the Mcl1 gene. This strain may be useful for generating conditional mutations in applications related to immune function and apoptosis of lymphocytes.

Detailed description

Mice that are homozygous for the targeted mutation are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The donating investigator indicates that homozygous males have severely reduced fertility for unknown reasons, while females have normal fertility. Endogenous protein expression is unaffected by the inserted loxP sequences. When bred to mice with a cre recombinase gene under the control of a promoter of interest, exon 1 of the targeted gene is deleted in the tissue of interest. These mutant mice may be useful in studying global, temporal, or tissue-specific deletion of the endogenous gene, particularly in studies of immune function, including apoptosis, B and T cell development, and bone marrow cell differentiation.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 004126), this mutant mouse strain may be useful in studies of lymphocyte development.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain expressing interferon inducible Cre recombinase in the lymphocytes (Stock No. 003556), this mutant mouse strain may be useful in studies of lymphocyte development.

Development

A targeting vector was designed to insert a loxP site upstream of transcriptional start ATG of the endogenous gene. An additional targeting vector was then used to insert a loxP-flanked cytomegalovirus (CMV) promoter driving the expression of a hygromycin–thymidine kinase fusion protein (HYG-Tk) into intron 1 of the endogenous gene. This construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells and then transiently transfected with CMV-Cre. Cre-mediated recombination resulting in a loxP-flanked exon 1 (and deletion of the HYG-Tk) were selected and injected into C57BL/6 blastocysts. Chimeric mice were crossed to C57BL/6 and the resulting heterozygotes were intercrossed to generate homozygotes prior to arrival at The Jackson Laboratory. These mice were crossed with "B6129F1" mice for at least one generation after arriving at The Jackson Laboratory.

Allele

Symbol: Mcl1^tm3Sjk
Name: targeted mutation 3, Stanley J Korsmeyer
MGI accession ID: MGI:2684151
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Mcl1
Marker name: myeloid cell leukemia sequence 1
Chromosome: 3
Strain of origin: 129X1/SvJ
Molecular note: Single loxP sites flank exon 1, which contains the start codon. Western blot analysis of lysates of thymocytes showed the level of protein in mutant mice to be comparable to that in wild-type mice.