• PMID: 13129914
• Gene Name: PAFAH1B1
• Condition: Associated with spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Associated with spermatogenesis

Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility

Nayernia K, Vauti F, Meinhardt A, Cadenas C, Schweyer S, Meyer BI, Schwandt I, Chowdhury K, Engel W, Arnold HH.

Lis1 protein is the non-catalytic component of platelet-activating factor acetylhydrolase 1b (PAF-AH 1B) and associated with microtubular structures. Hemizygous mutations of the LIS1 gene cause type I lissencephaly, a brain abnormality with developmental defects of neuronal migration. Lis1 is also expressed in testis, but its function there has not been determined. We have generated a mouse mutant (LIS1GT/GT) by gene trap integration leading to selective disruption of a Lis1 splicing variant in testis. Homozygous mutant males are infertile with no other apparent phenotype. We demonstrate that Lis1 is predominantly expressed in spermatids, and spermiogenesis is blocked when Lis1 is absent. Mutant spermatids fail to form correct acrosomes and nuclei appear distorted in size and shape. The tissue architecture in mutant testis appears severely disturbed displaying collapsed seminiferous tubules, mislocated germ cells, and increased apoptosis. These results provide evidence for an essential and hitherto uncharacterized role of the Lis1 protein in spermatogenesis, particularly in the differentiation of spermatids into spermatozoa. FAU - Nayernia, Karim AU - Nayernia K AD - Institute for Human Genetics and Department of Pathology, University of Göttingen, Göttingen 37073, Germany. FAU - Vauti, Franz AU - Vauti F FAU - Meinhardt, Andreas AU - Meinhardt A FAU - Cadenas, Christina AU - Cadenas C FAU - Schweyer, Stephan AU - Schweyer S FAU - Meyer, Barbara I AU - Meyer BI FAU - Schwandt, Iris AU - Schwandt I FAU - Chowdhury, Kamal AU - Chowdhury K FAU - Engel, Wolfgang AU - Engel W