The Mfsd14a gene, previous called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for β-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells suggesting that they may transport a solute from the bloodstream that is required for spermiogenesis.
Reproduction (Cambridge, England). 2016 Apr 22 [Epub ahead of print]
Joanne Doran, Cara Walters, Victoria Kyle, Peter Wooding, Rebecca Hammett-Burke, William H Colledge
J Doran, 418 Science Park, Takeda Cambridge Ltd, Cambridge, United Kingdom of Great Britain and Northern Ireland., C Walters, Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland., V Kyle, Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland., P Wooding, Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland., R Hammett-Burke, Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland., W Colledge, Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .