|Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility.|
|PMID: 13129914 Owner: NLM Status: MEDLINE|
|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.|
|Karim Nayernia; Franz Vauti; Andreas Meinhardt; Christina Cadenas; Stephan Schweyer; Barbara I Meyer; Iris Schwandt; Kamal Chowdhury; Wolfgang Engel; Hans-Henning Arnold|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-09-16|
|Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Nov|
|Created Date: 2003-11-24 Completed Date: 2004-01-12 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States|
|Languages: eng Pagination: 48377-85 Citation Subset: IM|
|Institute for Human Genetics and Department of Pathology, University of Göttingen, Göttingen 37073, Germany.|
|APA/MLA Format Download EndNote Download BibTex|
Acrosome / metabolism
Cell Nucleus / metabolism
Disease Models, Animal
Dyneins / biosynthesis
Infertility, Male / etiology*
Microtubule-Associated Proteins / biosynthesis*
Reverse Transcriptase Polymerase Chain Reaction
Spermatids / metabolism*
Testis / metabolism*
Tubulin / biosynthesis
|0/Microtubule-Associated Proteins; 0/Tubulin; EC 18.104.22.168/1-Alkyl-2-acetylglycerophosphocholine Esterase; EC 22.214.171.124/Pafah1b1 protein, mouse; EC 126.96.36.199/Dyneins|
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