B6;129-Slc9a3r1^tm1Ssl/J

Stock number: 012862
Research areas: Endocrine Deficiency Research, Internal/Organ Research

Description

In this strain the targeted allele replaces exon 1 of the endogenous mouse solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1) gene with a neomycin (neo) resistance cassette, abolishing gene function. These mice may be useful for studying renal, gastrointestinal, and hepatic transport.

Detailed description

In this strain exon 1 of the endogenous mouse solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1, or Nherf-1) gene is disrupted by a neomycin (neo) resistance cassette, abolishing gene function. No homozygous females are obtained in the first 3 generations of backcrosses. Nherf-1^-/- females obtained between F4 and F6 generations have 30-50% reduction in bodyweight over wildtype littermates, show impaired mobility, and some develop hydrocephaly. Most homozygous females die 30-35 days after birth due to reduced bone mineral density. Associated bone fractures are observed. Male homozygotes display an increase in urinary excretion of uric acid, a decrease in serum phosphate concentration, an increase in serum alkaline phosphatase, a 3-fold increase in urinary phosphate excretion, a slight increase in urinary magnesium excretion, but maintain normal overall renal function. Homozygotes also exhibit abnormalities in the targeting and signalling of a number of hormone receptors including the B2-adreneric receptor, the PTH1 receptor, the k-opiod receptor, and dopamine receptors. NHERF-1 heterozygous mice exhibit an intermediate phenotype,are viable, fertile, and normal in size. The donating investigator notes that colonies on a 129/SvJ background only yield 2-3 animals per litter. These mice may be useful for studying renal, gastrointestinal, and hepatic transport.

Development

A targeting vector was designed to replace exon 1 of the solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1) gene with a neomycin (neo) resistance 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 C57BL/6J blastocysts and the resulting chimeric mice were bred to C57BL/6J mice to generate a colony of Nherf-1^-/- mice. These mice were subsequently backcrossed at least 7 generations onto a C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 8 of 32 markers (on four different chromosomes) that were not C57BL/6J allele-type. These data suggest 129S genetic contamination prior to arrival at The Jackson Laboratory.

Allele

Symbol: Slc9a3r1^tm1Ssl
Name: targeted mutation 1, Shirish Shenolikar
MGI accession ID: MGI:2386785
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc9a3r1
Marker name: solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exon 1 was replaced by a neomycin selection cassette inserted by homologous recombination. Protein was undetected in homozygous mutant mice by Western blot analysis of kidney extracts and immunostaining of proximal renal tubules.