Homozygotes: A targeting vector was designed to insert a neomycin resistance (neo) cassette into the 3' end of exon 2 of the solute carrier family 9 (sodium/hydrogen exchanger), member 1 (Slc9a1 or Nhe1) gene, abolishing gene function. Nhe1 is expressed in the hippocampus, periamygdaloid cortex, and cerebellum, and is a key regulator of pH homeostasis, cell volume, and the proliferative response to growth factor stimulation. Homozygous Nhe1-/- mice are viable and indistinguishable from their littermates through the first week of age. These mice show decreased postnatal growth with ataxic gait and epileptic-like seizures at 2 weeks of age. Mortality of homozygous mutant mice is increased to 68% by 29 days of age, with a reduction to 10% under low stress conditions. Postmortem animals exhibit a waxy particulate in the ears, around the eyes and chin, and on the ventral surface of the paws. The thickness of the skin, including the epidermis, dermis, subcutaneous fat, and muscle is significantly thinner in these mutant mice. These mice also display thickening of the lamina propria and slight atrophic glandular mucosa in the stomach. These mice may be useful for studying postnatal cell proliferation and similarities between the Nhe-/- mutation and the spontaneous swe mutation within the Nhe locus.
Heterozygote: Heterozygous mice are viable, fertile, and normal in size. They exhibit normal growth and are phenotypically similar to wildtype mice.
