Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat hypogonadic (hgn/hgn) testes

• Published in: Reproduction (Cambridge, England) Vol. 132; no. 1; pp. 79 - 93
• Main Authors: Suzuki, Hiroetsu, Yagi, Mio, Suzuki, Katsushi
• Format: Journal Article
• Language: English
• Published: Colchester Society for Reproduction and Fertility 01.07.2006; BioScientifica Ltd; Portland
• Subjects: Amino Acid Sequence; animal models; Animals; antibodies; antigens; Apoptosis; Base Sequence; Biological and medical sciences; Biomarkers - analysis; Cell Cycle Proteins - genetics; Cell Proliferation; DNA, Complementary - analysis; exons; Fundamental and applied biological sciences. Psychology; Genetic Linkage; germ cells; Humans; Hypogonadism - pathology; Immunohistochemistry - methods; In Situ Nick-End Labeling; loci; Male; Mice; Mice, Mutant Strains; mitosis; Models, Animal; Molecular Sequence Data; Mutation; postpartum period; Rats; recessive genes; Reverse Transcriptase Polymerase Chain Reaction; seminiferous tubules; Sequence Alignment; Sequence Analysis, DNA; Sertoli cells; Sertoli Cells - pathology; Spindle Apparatus - ultrastructure; Staining and Labeling; Vertebrates: reproduction; Cell proliferation; Sertoli cell; Vertebrata; Reproduction; Mammalia; Rat; Animal; Rodentia; Microtubule associated protein; Mutation; Testicle; Male genital system
• ISSN: 1470-1626; 1741-7899
• DOI: 10.1530/rep.1.01104

Male rats with hypogonadism (hgn/hgn) experience sterility from testicular dysplasia, which is controlled by a single recessive gene, hgn. The postnatal growth of the seminiferous tubules was severely affected. In this study, we localized the hgn locus to a 320 kb region on rat chromosome 10 and detected the insertion of a 25 bp duplication into the sixth exon of the sperm-associated antigen 5 (Spag5/astrin/MAP126) gene, which codes for a microtubule-associated protein. This mutation results in a truncated Spag5 protein lacking the primary spindle-targeting domain at the C terminus. Immunological staining with antibodies to markers for Sertoli and germ cells during the early postnatal period indicated that the abnormal mitosis with dispersed chromosomes in hgn/hgn testes occurs in proliferating Sertoli cells. Therefore, apoptotic Sertoli cell death would result from the disorganization of the spindle apparatus caused by defective Spag5. These findings suggested that the Spag5 is essential for testis development in rats and that the hgn/hgn rat is a unique animal model for studying the function of Spag5.