Mice harboring the Msh2LoxP allele have loxP sites flanking exon 12 of the mutS homolog 2 (E. coli) gene [Msh2]. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding a portion of the essential ATPase domain of MSH2 protein deleted in the cre-expressing tissues.
Raju Kucherlapati, Brigham & Women's Hosp, Harvard Med Sch
The Msh2LoxP allele has loxP sites flanking exon 12 of the mutS homolog 2 (E. coli) [Msh2] gene. Homozygous Msh2LoxP mice are viable and fertile with no observed abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding a portion of the essential ATPase domain of MSH2 protein deleted in the cre-expressing tissue(s). These Msh2LoxP mice may be useful in generating tissue-specific MSH2 deletions for studying DNA mismatch repair (single-nucleotide and insertion/deletion mismatches), as well as tumor development.
For example, when Msh2LoxP mice are bred to a strain expressing Cre recombinase in embryonic tissues (EIIA-Cre; see Stock Nos. 003314 or 003724), the resulting mice with pan deletion of MSH2 exhibit high incidence of lymphoma.
Additionally, when Msh2LoxP mice are bred to Villin-Cre mice (see Stock No. 004586 for example), the resulting mice with MSH2 mismatch repair function inactivated in the intestinal mucosa exhibit intestinal adenomas/adenocarcinomas and somatic Apc mutations at tumor initiation. This allows modeling of the intestinal cancer features of Lynch Syndrome because the lymphoma phenotype of pan MSH2 knockout mice is greatly diminished with tumorigenesis restricted predominantly to the intestinal tract.
A targeting vector was designed to insert a loxP site and frt-flanked PGK-neo cassette upstream of exon 12, and a second loxP site downstream of exon 12 of the mutS homolog 2 (E. coli) [Msh2] gene. The donating investigator reports that the construct was electroporated into 129/Sv;C57BL/6J;SJL-derived WW6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females to establish the colony. To remove the frt-flanked PGK-neo cassette, the Msh2neoLoxP-FRT neo mice were then bred to mice expressing FLPe recombinase (unknown genetic background; see Stock Nos. 005703 or 003800). The resulting Msh2LoxP mice (with loxP site and single frt site remaining upstream of exon 12, and a second loxP site downstream of exon 12) were backcrossed to C57BL/6J mice for ten generations, and then bred together to generate homozygous mice prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 2.1, Raju Kucherlapati|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||M2CKO; MSH2CKO; MSH2CKO pGKneo flipped ou; Msh2LoxP|
|Gene Symbol and Name||Msh2, mutS homolog 2|
|Gene Synonym(s)||AI788990; COCA1; FCC1; HNPCC; HNPCC1; LCFS2; expressed sequence AI788990|
|Strain of Origin||STOCK 129/Sv and C57BL/6J and SJL|
|Molecular Note||An frt flanked neo cassette with a 5' loxP site was inserted upstream of exon 12, and an additional loxP site was inserted downstream of exon 12. Flp mediated recombination removed the neo cassette leaving exon 12 floxed.|
|Mutations Made By|| |
Raju Kucherlapati, Brigham & Women's Hosp, Harvard Med Sch
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