These Slc9a knockout mice exhibit decreased postnatal growth with ataxic gait, epileptic-like seizures, increased mortality, thin skin, thickening of the lamina propria and slight atrophic glandular mucosa in the stomach. These mice may be useful for studying postnatal cell proliferation.
Gary E Shull, University of Cincinnati
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.
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. The construct was electroporated into 129-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to Black Swiss females, and these mice were subsequently backcrossed to FVB/N mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ inbred mice for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Sheila M Bell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Nhe1 -; Nhe1-|
|Gene Symbol and Name||Slc9a1, solute carrier family 9 (sodium/hydrogen exchanger), member 1|
|Strain of Origin||Not Specified|
|Molecular Note||A portion of exon 2 was replaced by a neomycin selection cassette inserted by homologous recombination. The deleted region encoded transmembrane domains 6 and 7 (amino acids 217 through 275). Two aberrant transcripts were detected in mutant mice by Northern blot and RT-PCR analyses. Analysis indicated that a 613 bp transcript resulted from readthrough of the neo cassette and a 380 bp transcript underwent splicing of codon 198 to exon 3. Biochemical analysis, based on pH recover after an acute acid load, of acinar cells indicated a functional ablation of the endogenous protein.|
|Mutations Made By|| |
Shelia Bell, Children's Hospital of Cincinnati
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or FVB/NJ inbred mice. The Donating Investigator confirms mortality rate of homozygotes is 68% by 29 days of age, with a reduction to 10% under low stress conditions.
When using the Nhe1- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34264 in your Materials and Methods section.