B6.129S7(NOD)-Cr2^tm1Hmo/J

Stock number: 008225
Product name: CD21-KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

This Cr2 (CD21) knockout strain exhibits defective memory B cell differentiation and reduced levels of IgG and IgM. These mice may be suitable for use in studies of humoral immune response, the activation and proliferation of B cells and adult neurogenesis.

Detailed description

Complement receptor 2 is involved with immune homeostasis, specifically lymphocyte activation in primary immune responses to T dependent antigens and in the generation of memory B cells. In the mouse, complement receptors type 1 and type 2 are encoded by a single Cr2 gene by alternate splicing of a single RNA product.

Flow cytometry of spleen cells from homozygotes reveals the deficiency of complement receptors type 1 and type 2. Homozygotes exhibit reduced levels of IgG after immunization with a T-cell dependent antigen. In the hippocampus of homozygous mice, there is a 2 to 3 fold increase in immature neurons and an approximately 40% increase in mature neurons. Bacterial clearance is delayed and survival from pneumococcal infection is significantly reduced (only 20% survive) in homozygotes. Onset of scrapie (spongiform encephalopathy) is delayed after intraperitoneal inoculation of prions. In experimentally induced intestinal ischemia-reperfusion injury, there is less resulting tissue injury in mutant mice when compared to wildtype controls.

Mice that are homozygous for this targeted knock-out of the Cr2 gene are viable and fertile. No gene product (mRNA) is detected by Northern blot analysis.

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.

Development

A targeting vector designed by Dr. Hector Molina (Washington University School of Medicine, St. Louis, MO) containing a PGK-NEO cassette, pGKneobpA, was used to disrupt part of exon 1 and exon 2, encoding the short consensus repeat (SCR) 14. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission.

The mice were crossed to C57BL/6 for an unknown number of generations before being backcrossed to NOD for 13 generations. Upon arrival at The Jackson Laboratory in 2007, the mice at generation N13F5 on NOD were crossed to C57BL/6J (Stock No. 000664) for 5 or 6 generations, using a marker assisted protocol. Sperm was then cryopreserved.

Allele

Symbol: Cr2^tm1Hmo
Name: targeted mutation 1, Hector Molina
MGI accession ID: MGI:1932568
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cr2
Marker name: complement receptor 2
Chromosome: 1
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Molecular note: A PGK-neomycin resistance cassette replaced part of the first and all of the second exon encoding short consensus repeat (SCR) 14. Flow cytometry of spleen cells using three different rat antimouse CR2 monoclonal antibodies showed that homozygous mutant mice were deficient in the expression of the receptors.