These Abcc6 knock-out mice develop ectopic mineralization of connective tissue and may be useful in studies of connective tissue mineralization (calcinosis) and Pseudoxanthoma Elasticum (PXE).
Jouni Uitto, Thomas Jefferson University
Mice that are homozygous for this targeted mutation develop patchy, progressive mineralization of the dermis, kidneys, eyes, arteries, heart and subcutaneous tissues, mimicking the human disease symptoms of pseudoxanthoma elasticum. Mineralization of connective tissue capsule surrounding vibrissae is detectable at 5 weeks of age. Mineralization is associated with collagen fibrils and elastic fibers. Oxidative stress, as indicated by lipid peroxidation and protein oxidation, is higher in liver tissue and serum of mutant mice when compared to wildtype controls. Antioxidant diet reduces the oxidative stress levels in knock out mice, but does not prevent ectopic mineralization. The severity of mineralization can be altered by mineral intake as a diet with elevated magnesium levels prevents pathological connective tissue mineralization in mutants. Serum matrix gla protein (MGP) levels are reduced in homozygotes and the protein is under-carboxylated with diminished activity. Fetuin-A serum levels are also reduced. Homozygotes are viable, fertile, and normal in size. The Donating Investigator reports sporadic deaths of homozygotes up to 18 months of age. No gene product (mRNA) is detected by Northern blot analysis of total RNA from liver tissue of homozygotes. Heterozygotes do not develop ectopic mineralization of soft connective tissues. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
A targeting vector containing a NEO cassette was used to disrupt exons 15 through 18. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to C57BL/6J female mice. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for 5 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1 John F Klement|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Abcc6, ATP-binding cassette, sub-family C (CFTR/MRP), member 6|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A neomycin resistance gene replaced exons 15-18 of the locus. Transcript proved to be absent in Northern blot analysis.|
When maintaining a live colony, these mice can be bred as homozygotes. The Donating Investigator reports sporadic deaths of homozygotes up to 18 months of age.
When using the B6.129S1-Abcc6tm1Jfk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013787 in your Materials and Methods section.