B6.129S4-Cd48^tm1Rsr/EpaulJ

Stock number: 023536
Product name: Slamf2-/-
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Cd48 knock-out mice, on a congenic C57BL/6 background, develop auto-antibodies and glomerulonephritis. They are suitable for use in applications related to the study of T-cell tolerance and systemic lupus erythematosus.

Detailed description

The Cd48 gene, also know as Slamf2 (signaling lymphocytic activation molecule 2), encodes for a lymphocyte cell surface antigen that binds CD2 and CD244 and is involved in regulation of T cell activation. These mice carry a targeted mutation for Cd48, in which a NEO cassette has replaced the exon encoding the immunoglobulin-V-like domain (the binding domain for CD2). Mice that are homozygous for the targeted mutation are viable and fertile. No cell surface CD48 protein is detected by flow cytometric analysis of thymocytes and splenocytes from homozygous animals. Female homozygotes develop auto-antibodies by 3 months, and glomerulonephritis by 6 months of age. Homozygotes exhibit increased numbers of short term hematopoietic stem cells (HSC) and multipotent progenitor cells, while decreased numbers of myeloid progenitor cells. HSCs from homozygotes have impaired short term engraftment in transplantation studies, as well as defective proliferation (increased quiescence). Cytokine and interferon gamma levels in the bone marrow of homozygotes are significantly reduced. Homozygotes on the congenic C57BL/6 background have a shortened lifespan (most die by 80 weeks of age) compared to wildtype controls. By approximately 16 weeks of age, most homozygotes have developed tumors (predominantly lymphomas).

Development

A targeting vector designed by Dr. Arlene Sharpe (Harvard Medical School) containing a NEO cassette was used to disrupt the exon encoding the immunoglobulin-V-like domain. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for 12 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival at The Jackson Laboratory Repository, the mice were crossed to C57BL/6J inbred mice (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Cd48^tm1Rsr
Name: targeted mutation 1, Hans Reiser
MGI accession ID: MGI:2180770
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd48
Marker name: CD48 antigen
Chromosome: 1
Strain of origin: 129S4/SvJae
Molecular note: A neomycin selection cassette replaced the exon encoding the immunoglobulin-V-like domain, which forms a binding site for the Cd2 antigen. Thymocytes and splenocytes isolated from homozygous mutant mice were found to lack surface expression of the endogenous protien.