In this strain exon 1 of the endogenous mouseNherf1 (NHERF family PDZ scaffold protein 1 (formerly Slc9a3r1) 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.

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In this strain the targeted allele replaces exon 1 of the endogenous mouse Nherf1 (NHERF family PDZ scaffold protein 1 (formerly Slc9a3r1) gene with a neomycin (neo) resistance cassette, abolishing gene function. These mice may be useful for studying renal, gastrointestinal, and hepatic transport.

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