STOCK Stk4^tm1.1Rjo Stk3^tm1.1Rjo/J

Stock number: 017635
Product name: mst1^fl mst2^fl
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

These double floxed mutant mice possess loxP sites flanking exons 4-5 of the Stk4 gene and exons 5-6 of the Stk3 gene. This strain may be useful for generating conditional mutations in applications related to studies of cell proliferation, apoptosis, and tumorigenesis.

Detailed description

Stk4 (serine/threonine kinase 4 ) and Stk3 (serine/threonine kinase 3) are the mouse orthologs for the Drosophila hippo gene. Both Stk4 and Stk3 are key components of the Salvador-Warts-Hippo (SWH) pathway, which regulates tissue growth and organ size by restricting cell proliferation and promoting apoptosis. Mice that are homozygous for both the floxed targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 4-5 of the (Stk4) gene and exons 5-6 of the (Stk3) gene deleted in the cre-expressing tissue(s).

When bred to a strain with Cre recombinase expression in the liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of hepatocyte proliferation and liver cancer.

Development

For the Stk4^tm1.1Rjo (mst1) targeted mutation, a targeting vector containing an FRT flanked NEO cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 5 and loxP sites were inserted flanking exons 4 and 5. The construct was electroporated into (C57BL/6Brd-Tyr^c-Brd x 129S6/SvEvTac)F1-derived RJ2.2 embryonic stem (ES) cells. ES cells containing the construct were aggregated with CD1 morulae and the resulting chimeric males were bred with CD1 females for germline transmission. The mice were then bred to a FLPe recombinase expressing strain to remove the selection cassette. Heterozygotes that retained the loxP site flanked exons 4 and 5 were then intercrossed to generation homozygotes.

For the Stk3^tm1.1Rjo (mst2) targeted mutation, a targeting vector containing an FRT flanked NEO cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 6 and loxP sites were inserted flanking exons 5 and 6. The construct was electroporated into (C57BL/6Brd-Tyr^c-Brd x 129S6/SvEvTac)F1-derived RJ2.2 embryonic stem (ES) cells. ES cells containing the construct were aggregated with CD1 morulae and the resulting chimeric males were bred with CD1 females for germline transmission. The mice were then bred to a FLPe recombinase expressing strain to remove the selection cassette. Heterozygotes that retained the loxP site flanked exons 5 and 6 were then intercrossed to generation homozygotes.

The single mutant lines were then intercrossed to obtain this double mutant strain, which was maintained on a mixed background consisting of CD1, C57BL/6 and 129. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Stk4^tm1.1Rjo
Name: targeted mutation 1.1, Randy L Johnson
MGI accession ID: MGI:4430536
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Stk4
Marker name: serine/threonine kinase 4
Chromosome: 2
Strain of origin: (C57BL/6Brd-Tyr^c-Brd x 129S6/SvEvTac)F1
Molecular note: Exons 4 and 5 were floxed and an FRT flanked neo cassette placed in intron 5. The neo cassette was removed by flp-mediated recombination, leaving exons 4 and 5 flanked by loxP sites.

Allele

Symbol: Stk3^tm1.1Rjo
Name: targeted mutation 1.1, Randy L Johnson
MGI accession ID: MGI:4430537
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Stk3
Marker name: serine/threonine kinase 3
Chromosome: 15
Strain of origin: (C57BL/6Brd-Tyr^c-Brd x 129S6/SvEvTac)F1
Molecular note: Exons 5 and 6 were floxed and an FRT flanked neo cassette was placed in intron 6. The neo cassette was removed by flp-mediated recombination, leaving exons 5 and 6 flanked by loxP sites.