Mice homozygous for this targeted allele (Nf123a-/-) lack the alternatively spliced exon 23a (which modifies the GTPase-activating protein (GAP) domain of Nf1). These mutant mice may be useful for neurological studies of Neurofibromatosis Type I, growth, differentiation, and learning and memory.
Alcino J. Silva, University of California, Los Angeles
Mice homozygous for this targeted allele (Nf123a-/-) lack the alternatively spliced exon 23a (which modifies the GTPase-activating protein (GAP) domain of Nf1), and are viable and fertile. Protein and mRNA isolated from homozygous brain tissue shows normal type I (exon 1-21 containing)
neurofibromin isoform but absence of the alternatively spliced, exon 23a-containing type II neurofibromin isoform (which has a greater affinity for Ras but lower GAP activity than the type I isoform). Homozygotes have no reported increase in tumor predisposition, but show specific learning impairments in contextual discrimination, spatial learning, and coordination. These Nf123a-/- mutant mice may be useful for neurological studies of Neurofibromatosis Type I, growth, differentiation, and learning and memory.
A targeting vector was designed to replace 300 bp (including exon 23a) of the targeted gene with a neo cassette. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred with C57BL/6J females. These resulting Nf123a- mutant mice were then backcrossed to C57BL/6NTac for at least seven generations prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Camilyn Brannan|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Nf1, neurofibromin 1|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A neomycin resistance cassette replaced 300 bp of genomic DNA including exon 23a. RT-PCR analysis of brain detected neurofibromin type I but not the type II isoform in homozygous mutant mice. Western blot analysis detected the type I but not the type II neurofibronin in brain of homozygous mutant mice. Immunohistochemical analysis of brain did not detect type II neurofibromin isoform in homozygous mutant mice.|
|Mutations Made By|| |
Alcino Silva, University of California, Los Angeles
When maintaining a live colony, homozygous mice may be bred.
When using the B6.129S1-Nf1tm1Cbr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007923 in your Materials and Methods section.