B6.129S2-Slc34a1^tm1Hten/J

Stock number: 004802
Product name: Npt2-
Research areas: Cell Biology Research, Endocrine Deficiency Research, Internal/Organ Research

Description

These Slc34a1 knock-out mice exhibit severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.

Detailed description

Mice that are homozygous for the targeted mutation are viable and fertile, and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern blot analysis of bone, kidney, liver or lung, or by Western blot analysis of kidney. Homozygotes are smaller in size and have reduced weight compared to wildtype littermates. Secondary ossification defects revealed at weaning are followed by compensatory bone development. Mutant mice exhibit increased urinary excretion of inorganic phosphate and calcium, diet dependent hypercalciuria and hypercalcemia, as well as decreased serum parathyroid hormone levels, increased serum alkaline phosphatase activity, and elevated serum 1,25-dihyudroxyvitamin D. Homozygous mice do not respond to dietary challenges of low inorganic phosphate or parathyroid hormone content. Calcium and inorganic phosphate containing renal stones, nephrocalcinosis, are found in homozygotes at all ages. This mutant mouse strain may be useful in studies of hereditary hypophosphatemic rickets with hypercalciuria, HHRH, and familial hypercalciuria.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 6 to 10, encoding amino acids 178-389. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J and offspring were backcrossed to C57BL/6J for 9 generations.

Allele

Symbol: Slc34a1^tm1Hten
Name: targeted mutation 1, Harriet S Tenenhouse
MGI accession ID: MGI:2386786
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc34a1
Marker name: solute carrier family 34 (sodium phosphate), member 1
Chromosome: 13
Strain of origin: 129S2/SvPas
Molecular note: Exons 6 through 10 were replaced by a neomycin selection cassette inserted by homologous recombination. The deleted region encoded amino acids 178 through 389. Northern blot and RT-PCR analyses showed reduced levels of transcript in heterozygous mice and and an absence of transcript in homozygous mutant mice. While protein was undetected in homozygous mutant mice by Western blot analysis of renal tissue, normal levels of protein were detected in heterozygotes.