Sleep/wake function in Pannexin1 knockout and Pannexin1 ARG217HIS mutation mice.

In humans and other vertebrates Pannexins protein family was discovered by homology to invertebrate gap junctions proteins. Several other functions were also attributed to three vertebrate pannexins members. Six clinically significant independent variants of PANX1 gene lead to human oocyte development defects and infertility and ARG217HIS variant was reported in the case with pronounced symptoms of primary ovarian failure, severe intellectual disability, sensorineural hearing loss, and kyphosis. At the same time only mild phenotypes were observed in Pannexin1 knockout mice. In addition it was reported that a passenger mutation was identified in popular line of Pannexin1 knockout mice questioning what caused even those effects. So we reduplicated Pannexin1 mice knockout using the CRISPR/Cas9 method and reproduced one of the clinically significant substitutions (ARG217HIS) in mice model. In both cases no significant changes of phenotypes as size, weight, fertility etc. were observed. In addition we reproduced study on sleep/wake function in Pannexin1 knockout mice and found that previously reported effects were probably not caused by Pannexin1 knockout. We consider that the pathological role of PANX1, ARG217HIS substitution and some PANX1 functions in general calls for a reevaluation.