• PMID: 23495255
• Gene Name: GOLGA3
• Condition: Multiple spermatogenic defects
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Multiple spermatogenic defects

New point mutation in Golga3 causes multiple defects in spermatogenesis

Bentson LF, Agbor VA, Agbor LN, Lopez AC, Nfonsam LE, Bornstein SS, Handel MA, Linder CC.

Mice with repro27 exhibit fully penetrant male-specific infertility associated with a nonsense mutation in the golgin subfamily A member 3 gene (Golga3). GOLGA3 is a Golgi complex-associated protein implicated in protein trafficking, apoptosis, positioning of the Golgi and spermatogenesis. In repro27 mutant mice, a point mutation in exon 18 of the Golga3 gene that inserts a pre-mature termination codon leads to an absence of GOLGA3 protein expression. GOLGA3 protein was undetectable in the brain, heart and liver in both mutant and control mice. Although spermatogenesis in Golga3(repro27) mutant mice appears to initiate normally, development is disrupted in late meiosis during the first wave of spermatogenesis, leading to significant germ cell loss between 15 and 18 days post-partum (dpp). Terminal Deoxynucleotidyl Transferase dUTP-mediated Nick End Labeling analysis showed elevated DNA fragmentation in meiotic germ cells by 12 dpp, suggesting apoptosis as a mechanism of germ cell loss. The few surviving post-meiotic round spermatids exhibited abnormal spermiogenesis with defects in acrosome formation, head and tail development and extensive vacuolization in the seminiferous epithelium. Analysis of epididymal spermatozoa showed significantly low sperm concentration and motility and in vitro fertilization with mutant spermatozoa was unsuccessful. Golga3(repro27) mice lack GOLGA3 protein and thus provide an in vivo tool to aid in deciphering the role of GOLGA3 in Golgi complex positioning, cargo trafficking and apoptosis signalling in male germ cells. CI - © 2013 American Society of Andrology and European Academy of Andrology. FAU - Bentson, L F AU - Bentson LF AD - Department of Biology and Chemistry, New Mexico Highlands University, Las Vegas, NM 87701, USA. FAU - Agbor, V A AU - Agbor VA FAU - Agbor, L N AU - Agbor LN FAU - Lopez, A C AU - Lopez AC FAU - Nfonsam, L E AU - Nfonsam LE FAU - Bornstein, S S AU - Bornstein SS FAU - Handel, M A AU - Handel MA