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

Autor: Stephan Schweyer, Hans-Henning Arnold, Iris Schwandt, Barbara Meyer, Karim Nayernia, Wolfgang Engel, Franz Vauti, Kamal Chowdhury, Christina Cadenas, Andreas Meinhardt
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Male
Spermiogenesis
Cellular differentiation
Mutant
Apoptosis
medicine.disease_cause
Biochemistry
Mice
Exon
0302 clinical medicine
Tubulin
Testis
10. No inequality
0303 health sciences
Mutation
Reverse Transcriptase Polymerase Chain Reaction
Homozygote
Cell Differentiation
Spermatid differentiation
Exons
Immunohistochemistry
Spermatids
Cell biology
Phenotype
medicine.anatomical_structure
Female
Acrosome
Microtubule-Associated Proteins
medicine.medical_specialty
Genotype
Blotting
Western
Mice
Transgenic
DNA Fragmentation
Biology
03 medical and health sciences
Internal medicine
medicine
Animals
Spermatogenesis
Molecular Biology
Infertility
Male
Gene Library
030304 developmental biology
Cell Nucleus
Models
Genetic
Dyneins
Cell Biology
Blotting
Northern
Disease Models
Animal
Microscopy
Electron
Cell nucleus
Endocrinology
1-Alkyl-2-acetylglycerophosphocholine Esterase
030217 neurology & neurosurgery
Zdroj: The Journal of Biological Chemistry
Popis: 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.
Databáze: OpenAIRE
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