Allele Symbol: Ptpn11tm1Bgn
Name: targeted mutation 1, Benjamin G Neel
Alteration at locus: Targeted Mutation
ES Cell Line: J1 derived from B6;129S4
Homozygous phenotype: No homozygous mice are born, however, 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.
Heterozygous phenotype: Mice that are heterozygous for the targeted mutation are born at 50% less than predicted Mendelian ratios. 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.
Founder genetic background: 129S4/SvJae
Strain genetic background: B6;129S4
Strain Development: 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.
Suggested Control Mice: Wild-type littermates
Donor: Benjamin G. Neel, MD PhD, Ontario Cancer Institute
Araki T, Mohi MG, Ismat FA, Bronson RT, Williams IR, Kutok JL, Yang W, Pao LI, Gilliland DG, Epstein JA, Neel BG. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004 Aug;10(8):849-57. (Medline PMID: 15273746)
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable
Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email email@example.com.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
The donor or their institution limits the distribution to non-profit institutions only.
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|Litter||Recovered litter1; additional fees for any special requests.|
1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
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