Mice heterozygous for the Ptpn11D61G allele are born at 50% less than predicted Mendelian ratios for a het x het mating. Surviving heterozygotes are characterized by a decreased body size, a triangular facial appearance and multiple cardiac defects. By 5 months, heterozygotes develop leukocytosis, splenomegaly and a mild myeloproliferative disease. This mutant mouse strain may be useful in studies of Noonan syndrome.
Benjamin Neel, NYU School of MedicineRead More +
Mice that are heterozygous for the targeted mutation are born at 50% less than predicted Mendelian ratios for a heterozygote x heterozygote mating. No homozygous mice are born. At E11.5 all genotypes are represented at normal ratios, but by E13.5 homozygous embryos are reduced in number, have multiple cardiac defects and are grossly hemorrhagic with severe liver necrosis. Among E13.5 heterozygotes, 50% exhibit ventricular septal defects and enlarged valve primordia, but without myocardial thinning or edema and 50% exhibit mitral valve enlargement with normal hearts. Surviving heterozygotes reach at least 10 months of age. Similar to Noonan patients, heterozygous mice are characterized by a decreased body size and a triangular facial appearance. By 5 months, heterozygotes develop leukocytosis, splenomegaly and a mild myeloproliferative disease.This mutant mouse strain may be useful in studies of Noonan syndrome.
The targeting vector was designed (by site-directed mutagenesis) to change the Noonan syndrome associated mutation from aspartate to glycine at amino acid position 61 (D61G) and to insert a unique AgeI site in exon 3. A loxP-flanked pGK neomycin cassette was also inserted downstream of exon 3. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Transient Cre expression in targeted cells excised the neo cassette. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice and maintained as sibling matings. Upon arrival, mice were bred to C57BL/6 for at 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Benjamin G Neel|
|Allele Type||Targeted (Humanized sequence, Inserted expressed sequence)|
|Gene Symbol and Name||Ptpn11, protein tyrosine phosphatase, non-receptor type 11|
|Gene Synonym(s)||2700084A17Rik; 2700084A17Rik; AW536184; BPTP3; CFC; JMML; METCDS; NS1; PTP-1D; PTP1D; PTP2C; RIKEN cDNA 2700084A17 gene; SH-PTP2; SH-PTP3; SH2 domain-containing protein tyrosine phosphatase-2; SHP-2; SHP2; Shp2; Syp; expressed sequence AW536184|
|Promoter||Ptpn11, protein tyrosine phosphatase, non-receptor type 11, mouse, laboratory|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A D61G mutation was introduced into exon 3 by homologous recombination, as well as a floxed PGK-neo in intron 3. Transient Cre expression excised the neo, leaving the aspartate to glycine codon substitution. Southern blotting confirmed recombination and Western blotting indicated that expression of the mutant allele was normal.|
|Mutations Made By|| |
Benjamin Neel, NYU School of Medicine
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