Most embryos that are homozygous for this targeted mutation fail between embryonic days 6.5 and 7.0. Heterozygotes develop a variety of malignant tumors over the course of 10-30 months, including osteosarcoma (63%), lymphoma (15%), lung adenocarcinoma (10%), hepatocellular carcinoma (9%), and fibrosarcoma (9%). This strain may be useful in studies of embryonic development and cancer.
Dr. Tyler Jacks, Massachusetts Institute of Technology
Most embryos that are homozygous for this targeted mutation fail between embryonic days 6.5 and 7.0, exhibiting a collapsed extraembryonic region and the absence of organized extraembryonic ectoderm. The embryo proper continues to develop, but fails to initiate gastrulation. Heterozygotes develop a variety of malignant tumors over the course of 10-30 months, including osteosarcoma (63%), lymphoma (15%), lung adenocarcinoma (10%), hepatocellular carcinoma (9%), and fibrosarcoma (9%). A high rate of metastasis to distant sites such as the lung and liver was found. Schwannomas, meningiomas and ependymomas were not detected. RT-PCR analysis and sequencing of the product have shown that a mutant form of mRNA is transcribed and spliced. Immunoblotting fails to detect any full-length or shortened protein products, however. This strain may be useful in studies of embryonic development and cancer.
A targeting vector was designed to replace the 3' half of exon 2, all of exon 3, and the intervening intronic sequences with a neomycin resistance gene in opposite orientation. The targeting vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Resultant chimeric animals were crossed with C57BL/6. The strain was been maintained on a mixed 129S2/SvPas and C57BL/6 mixed background by the donating laboratory.
|Allele Name||targeted mutation 1, Tyler Jacks|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Merlin-; Nf2-; Nf2KO2-3|
|Gene Symbol and Name||Nf2, neurofibromin 2|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The 3' half of exon 2, all of exon 3 and intervening sequences were replaced by a neomycin cassette inserted in the reverse transcriptional orientation to the gene. RT-PCR analysis demonstrated that an aberrant transcript was expressed from this allele that spliced exon 1 to exon 5. However, immunoblot analysis on extracts derived from homozygous ES cells demonstrated that no stable mutant protein was detectable.|
|Mutations Made By|| |
Dr. Tyler Jacks, Massachusetts Institute of Technology
When maintained as a live colony, heterozygotes may be bred.
When using the B6;129S2-Nf2tm1Tyj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008190 in your Materials and Methods section.
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