Abnormal Sperm Development in pcd3J-/- Mice: the Importance of Agtpbp1 in Spermatogenesis

Abstract

Homozygous Purkinje cell degeneration (pcd) mutant males exhibit abnormal sperm development. Microscopic examination of the testes from pcd(3J)-/- mice at postnatal days 12, 15, 18 and 60 revealed histological differences, in comparison to wild-type mice, which were evident by day 18. Greatly reduced numbers of spermatocytes and spermatids were found in the adult testes, and apoptotic cells were identified among the differentiating germ cells after day 15. Our immunohistological analysis using an antihuman AGTPBP1 antibody showed that AGTPBP1 was expressed in spermatogenic cells between late stage primary spermatocytes and round spermatids. A global gene expression analysis from the testes of pcd(3J)-/- mice showed that expression of cyclin B3 and de-ubiquitinating enzymes USP2 and USP9y was altered by >1.5-fold compared to the expression levels in the wild-type. Our results suggest that the pcd mutant mice have defects in spermatogenesis that begin with the pachytene spermatocyte stage and continue through subsequent stages. Thus, Agtpbp1, the gene responsible for the pcd phenotype, plays an important role in spermatogenesis and is important for survival of germ cells at spermatocytes stage onward.

Alterations in the balance of tubulin glycylation and glutamylation in photoreceptors leads to retinal degeneration

“…By comparing the Ttll3 −/− and pcd (Ccp1 −/− ) mouse models, we demonstrate that the degree of deregulation of these PTMs correlates with the severity of the resulting retinal degeneration. Our work thus demonstrates how alterations in different tubulin-modifying enzymes can generate a range of phenotypic alterations, from a slowly progressing degeneration of the retina in Ttll3 −/− mice to a massive retinal degeneration accompanied by neurodegeneration and male infertility in pcd mice (Kim et al, 2011;Mullen et al, 1976;Mullen and LaVail, 1975). The demonstration that the functions of connecting cilia in photoreceptors are, similar to motile cilia and flagella, dependent on tubulin glycylation, further underlines the universal importance of this specific PTM for different types of cilia in the mammalian organism.…”

Exome Sequencing RevealsAGBL5as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families

“…The high RNA expression levels of Agbl5 in testis of P10 and P28 mice are in line with previously reported AGTBP1 expression where stronger antibody signals were detected in mouse testis from P18 onwards when compared to earlier stages. 56 This emphasizes an involvement of AGBL5 in spermatogenesis similarly to pcd-mice lacking AGTBP1 expression, showing infertility and abnormal sperm shape and motility. 14,16,56 Several AGBL5/Agbl5 splice variants are comprised in the Ensembl database but most of them are not yet experimentally confirmed.…”

“…56 This emphasizes an involvement of AGBL5 in spermatogenesis similarly to pcd-mice lacking AGTBP1 expression, showing infertility and abnormal sperm shape and motility. 14,16,56 Several AGBL5/Agbl5 splice variants are comprised in the Ensembl database but most of them are not yet experimentally confirmed. We revealed cDNA sequences in human retina missing exon 2 as well as sequences in human lymphocytes and muscle with an additional exon that is not present in the retina.…”

Genetics of Cerebellar and Neocortical Expansion in Anthropoid Primates: A Comparative Approach

“…For example, when disrupted, several of the genes highlighted by our analyses affect the development of multiple organs. For example, both AGTPBP1 and PAFAH1B have known roles in spermatogenesis [Yan et al, 2003;Kim et al, 2011], whilst disruption of PCNT can affect global somatic growth [Rauch et al, 2008]. If these genes do have an evolutionary role in cerebellar development, how are these pleiotropic effects avoided?…”