These Lyn knock-out mice exhibit abnormalities in the B cell lineage and in mast cell function. B-cell numbers are reduced in peripheral blood and secondary lymphoid tissues as well as in the recirculating B-cell population of the bone marrow.
IMR Colony, The Jackson Laboratory
Mice homozygous for the Lyntm1Sor targeted mutation are viable and fertile. Mutant mice display abnormalities in the B cell lineage and in mast cell function. B-cell numbers are reduced in peripheral blood and secondary lymphoid tissues as well as in the recirculating B-cell population of the bone marrow, but pro-B, pre-B and immature B-cell numbers in the bone marrow are the same as in wild type mice. Despite their reduced B-cell numbers, Lyn-deficient mice have elevated levels of serum IgM. Homozygotes accumulate plasma cells with age and produce autoantibodies specific for nuclear antigens and double stranded (ds) DNA. They develop severe glomerulonephritis as a result of IgG immune complex deposition in the kidneys. Aged Lyn-deficient mice also exhibit splenomegaly and have an expanded population of B lymphoblasts of the B1 lineage. B-cells from lymph nodes and spleen of Lyn-deficient mice respond poorly to LPS activation as well as to cross linking of immunoglobulin by anti-IgM antibody. Defects in mast cell function are manifested in a reduced IgE mediated anaphylactic response. Lyn-deficient mice are useful in studying the role of Lyn in immunoglobulin mediated signaling.
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.
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. This construct was electroporated into ES cells, and clones that had undergone homologous recombination into the active locus were selected for blastocyst injection. This strain was backcrossed to C57BL/6J using the marker assisted protocol designed by JAX Services at The Jackson Laboratory.
|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