B6.129X1-Cd2ap^tm1Shaw/J

Stock number: 008907
Research areas: Developmental Biology Research, Internal/Organ Research

Description

Homozygous Cd2ap, CD2-associated protein targeted mutant mice die at approximately 6 weeks of age. Cardiac hypertrophy, splenic and thymic atrophy, and ascites may be found upon postmortem examination. Proteinuria can be detected as early as 2 weeks of age, indicating kidney dysfunction. Heterozygotes show increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes.

Detailed description

Homozygous targeted mutant mice begin to show growth retardation at about 3 weeks of age, and die at approximately 6 weeks. Cardiac hypertrophy, splenic and thymic atrophy, and ascites may be found upon postmortem examination. Proteinuria can be detected as early as 2 weeks of age, indicating kidney dysfunction. The predominant kidney pathology involves glomeruli which become sclerotic by 4 weeks. CD2AP protein is not detected in the thymus, kidney, liver or spleen of homozygous targeted animals. Naive and cultured T cells show increased sensitivity to antigen, increased proliferation, increased number of cell divisions and increased apoptosis compared to wild type cells. Heterozygotes show increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes.

Development

Exon 2, encoding the first SRC homology 3 (SH3) domain, was replaced with a neomycin resistance cassette using 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Mice were backcrossed to C57BL/6 fifteen times by the donating laboratory.

Allele

Symbol: Cd2ap^tm1Shaw
Name: targeted mutation 1, Andrey S Shaw
MGI accession ID: MGI:2664945
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd2ap
Marker name: CD2-associated protein
Chromosome: 17
Strain of origin: 129X1/SvJ
Molecular note: The sequences encoding the first SRC homology 3 domain was replaced with a neomycin-resistance gene. Immunoblots of kidney, liver, spleen, and thymus proteins from homozygous mice indicated the absence of gene product.
General note: Heterozygous mutant mice exhibit highly organized microtubular deposits in the mesangium which is characteristic in human immunotactoid glomerulopathy (J:84748).