This model of familial tumoral calcinosis carries a Galnt3 knockout allele which is associated with hyperphosphatemia and low levels of intact FGF23. Mice develop ectopic calcification on a high phosphate diet.
Michael J. Econs, Indiana University School of Medicine
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), klotho (KL), and uridine diphosphate-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3).
Exons 2 and 3 of the mouse Galnt3 gene were deleted in this targeted knockout allele. The absence of protein expression was confirmed by western blot analysis on kidney extracts.
Mice lacking the protein develop hyperphosphatemia without apparent calcifications. Fgf23 expression is increased in bone of homozygous mice. Compared with wild-type and heterozygous littermates, homozygous mice have only about half of circulating intact FGF23 protein levels and higher levels of C-terminal fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Ectopic calcification develops on high phosphate diet.
Renal expression of sodium-phosphate cotransporters and K1 are elevated in
Galnt3-deficient mice. Galnt3-deficient males show infertility on the backcrossed C57BL/6 background. Both males and females show increased bone mineral density.
Exons 2 and 3 were replaced with a loxP-flanked neomycin cassette via homologous recombination in 129S/SvEv-derived embryonic stem (ES) cells. Resultant mice were crossed with EIIa-cre recombinase-expressing mice (see Stock No. 003724) to excise the neomycin cassette, then backcrossed to C57BL/6J for 8 generations by the donating lab.
|Allele Name||targeted mutation 1, Michael J Econs|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Galnt3, polypeptide N-acetylgalactosaminyltransferase 3|
|Strain of Origin||129S/SvEv|
|Molecular Note||Exons 2 and 3 were replaced with an loxP-flanked neo cassette. Cre-mediated recombination removed the neo cassette. The absence of protein expression was confirmed by western blot analysis on kidney extracts.|
Heterozygous males and females and homozygous females are viable and fertile. Homozygous males show growth retardation and infertility.
When using the Galnt3 deficient mouse strain in a publication, please cite the originating article(s) and include JAX stock #028318 in your Materials and Methods section.