STOCK Nf1^tm1Par/J

Stock number: 017639
Product name: Nf1flox
Research areas: Cancer Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

These Nf1^flox mice possess loxP sites flanking exons 31-32 of the neurofibromatosis 1 gene (Nf1), and have applications in studying cancer, neural crest development and neurofibromatosis type I.

Detailed description

Mutation in the human neurofibromin gene, NF1, is the cause of the autosomal dominant disorder Type I Neurofibromatosis. These mice possess loxP sites on either side of exons 31 and 32 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 31 and 32 deleted in the cre-expressing tissue(s).

When bred to a strain with Cre recombinase expression in the developing neural tube (see Stock No. 009107 for example), this mutant mouse strain may be useful in studies of Type I Neurofibromatosis.

When bred to a strain with Cre recombinase expression in neuronal cells (see Stock No. 003966 for example), this mutant mouse strain may be useful in studies of cerebral cortex development and reactive astrogliosis.

When bred to a strain with Cre recombinase expression in endothelial cells (see Stock No. 008863 for example), this mutant mouse strain may be useful in studies of neural crest development.

When bred to B6.Cg-Tg(Prrx1-cre)1Cjt/J mice (Stock No. 005584), mesenchyme-specific cre-expression results in mice that exhibit an increase in the amount of connective tissue, as well as muscle dystrophy characterized by fibrosis, a reduced number of muscle fibers, and reduced muscle force.

When bred to mice carrying Tg(Mx1-cre)1Cgn (Stock No. 003556), interferon-induced Cre-mediated recombination results in a progressive myeloproliferative disorder.

This allele is also part of the MADM-TG,p53KO,NF1-flox strain (Stock No. 017530), which is a genetic mosaicism model for cancer.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a loxP site and a PGKNeo cassette was inserted upstream of exon 31. A second loxP site was inserted downstream of exon 32. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then crossed to several other mutant lines. The combination mutant strain, with a mix of CD1, C57BL/6 and 129 genetic backgrounds, was crossed to C57BL/6J to separate the Nf1^tm1Par allele.

Allele

Symbol: Nf1^tm1Par
Name: targeted mutation 1, Luis F Parada
MGI accession ID: MGI:2176057
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Nf1
Marker name: neurofibromin 1
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Site of expression: When mice carrying this allele are mated to a Synapsin I promoter driven Cre transgenic mouse strain, NF1 function is abated in most differentiated neuronal populations, resulting in abnormal development of the cerebral cortex.
Molecular note: A loxP-neomycin selection cassette was inserted into intron 30 and a single loxP site was inserted into intron 32.