title: Ectopic expression of KitD814Y in spermatids of transgenic mice, interferes with sperm morphogenesis.
abstract: Kit is a receptor tyrosine kinase that plays a fundamental role during the development of germ cells. Additionally, a truncated product, tr-kit, expressed in haploid spermatids and mature spermatozoa can induce parthenogenetic activation when microinjected into mouse eggs, through the activation of PLCgamma-1. In this work, we induced ectopic expression of a mutated Kit protein, Kit(D814Y) during germ cell development. The in vivo expression of this mutant in spermatids produced malformations in mature spermatozoa, and in the most severe cases, sterility. Ultrastructural analysis indicated that condensing spermatids in the transgenic mouse presented a mislocalization of the manchette; a structure that has a crucial role during the elongation steps of spermiogenesis. This morphogenetic phenotype was accompanied by an increased phosphorylation of PLCgamma-1 in spermatogenic cells. Interestingly, we also found that, in wild-type testis, PLCgamma-1 is specifically phosphorylated in condensing spermatids, coincident with the timing of expression of tr-kit in spermiogenesis. We propose that alterations of PLCgamma-1 activity artificially promoted by ectopic Kit(D814Y) expression are related to the abnormalities of spermiogenesis. Our observations suggest that PLCgamma-1 activity could be involved in the shaping of spermatozoa.
authors.affiliation: Departamento de Fisiología Molecular y Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62271, México.
authors.forename: Denhí
authors.initials: D
authors.lastname: Schnabel
authors.forename: Laura
authors.initials: L
authors.lastname: Ramírez
authors.forename: Marina
authors.initials: M
authors.lastname: Gertsenstein
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.forename: Hilda
authors.initials: H
authors.lastname: Lomelí
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D051966:Phospholipase C gamma; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019009:Proto-Oncogene Proteins c-kit; C045073:Cre recombinase; D019426:Integrases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse; D010738:Type C Phospholipases; D051966:Phospholipase C gamma