129(B6)-Ccni^tm1Jro/J

Stock number: 006616
Product name: cyclin I KO
Research areas: Apoptosis Research, Internal/Organ Research

Description

In these knock-out reporter mice LacZ is primarily expressed in the glomerulus of podocytes in the kidney.

Detailed description

Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. No protein product from the targeted gene is detected in the tissues tested. Distinct lacZ staining is seen in the glomerulus of podocytes in the kidney. Weaker and variable expression of lacZ is seen in tubular cells. Increased susceptibility to apoptosis both in vitro and in vivo is observed. Following induction of experimental glomerulonephritis, podocyte apoptosis was increased 4-fold in homozygotes, which is associated with dramatically decreased renal function. This mutant mouse strain represents a model that may be useful in studies of apoptosis, renal impairment and glomerulosclerosis.

Development

A targeting vector containing neomycin resistance and beta-galactosidase genes was used to disrupt the gene. The construct was electroporated into AK7 129S4/SvJaeSor-derived embryonic stem (ES) cells. Correctly targeted cells were microinjected into C57BL/6J blastocysts. Resulting chimeric animals were backcrossed once to C57BL/6 and then crossed to 129 for six generations (N=6) by the donating laboratory.

Allele

Symbol: Ccni^tm1Jro
Name: targeted mutation 1, James M Roberts
MGI accession ID: MGI:3693371
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Ccni
Marker name: cyclin I
Chromosome: 5
Strain of origin: 129S4/SvJaeSor
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: The region of the gene encompassing all the coding exons except a small portion of the last exon was replaced by bacterial neomycin resistance and lacZ genes. No protein product from the targeted gene is detected by immunoblot analysis in tissue extracts of homozygous mutant 14- or 18-days post coitum (dpc) embryos or in mouse embryonic fibroblasts (MEFs) cultured from homozygous 13 dpc embryos. The highest levels of beta-galactosidase expression are detected by immunohistochemical analysis in brain, followed by testis, of one-month-old pups. In the kidney, distinct staining for beta-galactosidase is seen in a podocyte distribution in the glomerulus, and weaker, variable beta-galactosidase expression is seen in cells of the tubules.