The Kcp gene is disrupted by an inserted lacZ sequence in this line. These mutant mice may be useful for studying the pathology of renal fibrotic disease, as well as the role of KCP in bone morphogenetic protein (BMP) signaling during embryonic development, differentiation and disease.
Gregory R Dressler, University of Michigan
This Kcp-knockout allele has exons 2-21 (encoding amino acids 67-774) of the kielin/chordin-like protein locus (Kcp) replaced with an in-frame β-galactosidase gene (lacZ). The donating investigator reports no lacZ expression from the mutant allele is observed. No Kcp transcripts are observed in homozygous kidneys. Homozygous mice on a C57BL6;129 hybrid genetic background are viable and fertile. Homozygous null mice display increased sensitivity to induced renal injury using both the unilateral ureteral obstruction model of fibrosis and the folic acid model of acute tubular necrosis.
A targeting vector was designed to replace exons 2-21 (encoding amino acids 67-774) of the kielin/chordin-like protein locus (Kcp) with an in-frame insertion of a β-galactosidase (lacZ) gene and neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6 females to establish the mutant colony. Mutant mice were subsequently bred to wildtype mice for several generations, and mutant mice on a mixed C57BL/6;129 genetic background were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish The Jackson Laboratory Repository colony.
|Allele Name||targeted mutation 1, Gregory R Dressler|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcp, kielin/chordin-like protein|
|Site of Expression||No Kcp transcripts are observed in homozygous kidneys. Homozygous null mice are more susceptible to developing renal interstitial fibrosis and are more sensitive to tubular injury.|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Exons 2-21, encoding amino acids 67-774, were replaced with a lacZ-neomycin cassette. Absence of transcript in mutants was confirmed by Northern blot and RT-PCR.|
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129-Kcptm1Gdr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018296 in your Materials and Methods section.