B6.129S(Cg)-Galnt3^tm1Mjec/J

Stock number: 028318
Product name: Galnt3 deficient
Research areas: Developmental Biology Research, Internal/Organ Research, Metabolism Research, Reproductive Biology Research

Description

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.

Detailed description

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.

Development

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

Symbol: Galnt3^tm1Mjec
Name: targeted mutation 1, Michael J Econs
MGI accession ID: MGI:4355571
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Galnt3
Marker name: polypeptide N-acetylgalactosaminyltransferase 3
Chromosome: 2
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.