These p59fynT mice lack FYN expression in the hematopoietic system. They may have applications in studies related to TCR-induced lymphocyte activation.
Paul Stein, SRI International
A neo cassette in reverse orientation replaces exon 7b of the endogenous Fyn proto-oncogene (Fyn) in this strain. Fyn is a member of the Src family of non-receptor protein tyrosine kinases which plays a role in many cell processes including cell survival, T and B cell receptor signaling, growth factor and cytokine receptor signaling, and ion channel function. Transcripts of Fyn containing the alternatively spliced exon 7b, p59fynT, are found only in hematopoietic lineages while transcripts containing exon 7a (FynB) are found in all other tissues, with notably high levels in the brain. Mice homozygous for this allele are viable and fertile. These mice fail to express p59fyn in the hematopoietic system, yet still express FYN elsewhere in the body. Specifically, they have very few natural killer T (NKT) cells, altered Th17 development, and exhibit compromised T cell receptor (TCR) signaling and B cell responses.
A targeting vector was designed to replace exon 7b of the Fyn proto-oncogene (Fyn) with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S2/SvPas-derived D3J8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6NTac females. These mice were backcrossed to C57BL/6NTac mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation.
|Allele Name||targeted mutation 1, Roger M Perlmutter|
|Allele Type||Targeted (Modified isoform(s))|
|Allele Synonym(s)||fynT; p59fyn; p59fynT|
|Gene Symbol and Name||Fyn, Fyn proto-oncogene|
|Strain of Origin||129S2/SvPas|
|General Note||ES cell line = D3J8.|
|Molecular Note||A neo-derived cassette was used to replace exon 7b via homologous recombination, disrupting the thymic isoform of this gene while leaving the brain isoform intact. Western blot and immunoprecipitation did not detect protein product in thymocytes or splenocytes of homozygous mutant animals but protein product was present in brain. In Northern blot, mutant transcripts were detected in thymus whereas wild-type transcripts were detected in brain, proving successful knock out of the thymic isoform.|
|Mutations Made By|| |
Dr. Roger Perlmutter, Amgen
When maintaining a live colony, homozygous mice may be bred together.
When using the B6N.129S2-Fyntm1Rmp/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018154 in your Materials and Methods section.