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 Medicine
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
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.