These Lyn knock-out mice exhibit a reduced number of peripheral B cells; splenic B cells have enhanced mitogen-activated protein (MAP) kinase activation and an increased proliferative response to B cell antigen receptor (BCR) engagement.
Dr. Philippe Soriano, Mount Sinai School of Medicine
Mice homozygous for the Lyntm1Sor targeted mutation are viable and fertile. However, age-related autoimmunity has been observed in homozygotes which may make it preferable to maintain the strain heterozygously, at least on a 129 background. Lyn-deficient mice are useful in analyzing the role of Lyn in B cell antigen receptor (BCR) signaling. Mutant mice have a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged homozygotes develop splenomegaly, produce autoantibodies, and have an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from young homozygotes initiate early BCR signaling events, although in a delayed fashion. B cells exhibit an enhanced MAP kinase activation and an increased proliferative response to BCR engagement.
A gene targeting construct that deleted exons 3-7 of the active gene and replaced these sequences with a pol2s-neo expression cassette was used. TThe construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred. At The Jackson Laboratory mice were crossed to 129S1/SvImJ.
|Allele Name||targeted mutation 1, Philippe Soriano|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lyn, LYN proto-oncogene, Src family tyrosine kinase|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||A neomycin resistance cassette replaced exons 3 - 7 of the gene. No transcript for the targeted gene was detected on Northern blots from homozygous mutant mouse bone marrow cells.|
|Mutations Made By|| |
Dr. Philippe Soriano, Mount Sinai School of Medicine
The investigator maintains the colony by heterozygous matings. An autoimmune-like disease is observed in homozygotes. The expected coat color from breeding is black and white-bellied agouti.
When using the lyn- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003204 in your Materials and Methods section.
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