Ectopic expression of KitD814Y in spermatids of transgenic mice, interferes with sperm morphogenesis

• Published in: Developmental dynamics Vol. 233; no. 1; pp. 29 - 40
• Main Authors: Schnabel, Denhí, Ramírez, Laura, Gertsenstein, Marina, Nagy, Andras, Lomelí, Hilda
• Format: Journal Article
• Language: English
• Published: New York Wiley‐Liss, Inc 01-05-2005
• Subjects: Animals; differentiation; Gene Expression Regulation - physiology; Infertility, Male - genetics; Infertility, Male - metabolism; Integrases - metabolism; Intracellular Signaling Peptides and Proteins; KitD814Y; Male; manchette; Mice; Mice, Transgenic; Mutation; Phospholipase C gamma; phospholipase Cγ‐1; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - metabolism; Proto-Oncogene Proteins c-kit - biosynthesis; Proto-Oncogene Proteins c-kit - genetics; Spermatids - cytology; Spermatids - metabolism; spermatogenesis; Spermatogenesis - genetics; Spermatogenesis - physiology; Spermatozoa - cytology; Spermatozoa - physiology; transgenic mice; Type C Phospholipases - metabolism
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.20292

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 PLCγ‐1. In this work, we induced ectopic expression of a mutated Kit protein, KitD814Y 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 PLCγ‐1 in spermatogenic cells. Interestingly, we also found that, in wild‐type testis, PLCγ‐1 is specifically phosphorylated in condensing spermatids, coincident with the timing of expression of tr‐kit in spermiogenesis. We propose that alterations of PLCγ‐1 activity artificially promoted by ectopic KitD814Y expression are related to the abnormalities of spermiogenesis. Our observations suggest that PLCγ‐1 activity could be involved in the shaping of spermatozoa. Developmental Dynamics 233:29–40, 2005. © 2005 Wiley‐Liss, Inc.