STOCK Ptpn11^tm1.1Wbm/J

Stock number: 025758
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Shp2^fl floxed mice may be useful for studying Schwann cell regulation of axon outgrowth and myelination.

Detailed description

These SHP2^fl/fl mutant mice possess loxP sites flanking exons 3-4 of the protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) gene. PTPN11 encodes SHP2, which is implicated in tumor formation and regulates cell migration, proliferation, survival, and differentiation, epithelial-mesenchyal-transition (EMT), and senescence. Mutations in this gene have been associated with Noonan and Leopard syndromes, characterized by cardiac disease, and craniofacial, brain, and skin abnormalities. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissues.

For example, when bred to STOCK Tg(Wnt1-cre)11Rth/J mice (Stock No. 003829) expressing Cre Recombinase in neural crest cells, resulting homozygous mice were embryonic lethal beginning at E13.5 and have decreased numbers of Schwann cells and neural crest cells, and have defects in axon outgrowth and myelination. They also exhibit craniofacial and pigmentation abnormalities.

When bred to FVB(Cg)-Tg(Dhh-cre)1Mejr/J mice (Stock No. 012929) expressing Cre Recombinase in Schwann cells, resulting mice have decreased numbers of Schwann cells and defects in myelination.

Development

A targeting vector was designed to insert a loxP site upstream of exon 3 and a second loxP site followed by a frt-flanked neomycin resistance (neo) cassette, downstream of exon 4 of the protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) gene. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with C57BL/6 mice. Subsequently, they were bred to B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and Shp2^fl mice were subsequently backcrossed for 4 generations to FVB/N mice. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. Eight markers throughout the genome were segregating with C57BL/6 and 129, suggesting an incomplete backcross.

Allele

Symbol: Ptpn11^tm1.1Wbm
Name: targeted mutation 1.1, Walter Birchmeier
MGI accession ID: MGI:4365539
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ptpn11
Marker name: protein tyrosine phosphatase, non-receptor type 11
Chromosome: 5
Strain of origin: 129P2/OlaHsd
Molecular note: A loxP site was inserted upstream of exon 3 and an frt flanked neo cassette with a 5' loxP site was inserted downstream of exon 4. The neo cassette was removed by germ line, flp mediated recombination.