AQP4- knock-out mice have a neo cassette replacing part of exon 1 and part of intron 1 of the aquaporin 4 (Aqp4) gene, abolishing endogenous gene expression. Aquaporins are integral membrane proteins that function as water channel proteins that permit passive transport of water along an osmotic gradient. AQP4 is specifically expressed in the brain where it supports water homeostasis in neural tissue. The protein is also localized to the sarcolemma, cytoplasm, and basolateral plasma membrane, and respiratory system. AQP4 plays a role in cerebrospinal fluid (CSF) production and homeostasis, neuromuscular function, the urinary concentrating mechanism, airway hydration, and fecal dehydration. Northern blot analysis of brain homogenates from homozygous mutant mice show minimally detectable truncated Aqp4 transcripts. Western blots of brain homogenates from homozygous mutant mice show no detectable protein. Homozygous mice are viable and fertile and grossly normal in terms of survival, physical appearance, and organ morphology on this C57BL/6J congenic background. They exhibit reduced urine osmolality after water deprivation. The donating laboratory has made a suite of aquaporin knock-out mice available: AQP1- knock-out mice (Stock No. <a href="https://www.jax.org/strain/041861">041861</a>) lack exon 1 and part of intron 1 of Aqp1. AQP4- knock-out mice (Stock No. <a href="https://www.jax.org/strain/041862">041862</a>) lack part of exon 1 and part of intron 1 of Aqp4. AQP5- knock-out mice (Stock No. <a href="https://www.jax.org/strain/041863">041863</a>) lack exons 2 and 4, all of exon 3, and all of introns 2 and 3 of Aqp5.

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AQP4- knock-out mice have a neo cassette replacing part of exon 1 and part of intron 1 of the aquaporin 4 (Aqp4) gene, abolishing endogenous gene expression. These mice may be useful for studying disorders involving the imbalance of fluid movement in many systems including neural, ocular, and cardiovascular.