Document Detail


Disruption of a spermatogenic cell-specific mouse enolase 4 (eno4) gene causes sperm structural defects and male infertility.
MedLine Citation:
PMID:  23446454     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4(+/Gt)). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4(Gt/Gt)) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4(Gt/Gt) mice compared to wild-type mice. Sperm from Eno4(Gt/Gt) mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm.
Authors:
Noriko Nakamura; Qunsheng Dai; Jason Williams; Eugenia H Goulding; William D Willis; Paula R Brown; Edward M Eddy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-11
Journal Detail:
Title:  Biology of reproduction     Volume:  88     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-11-06     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Gene Expression
Infertility, Male / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutagenesis / physiology
Organ Specificity / genetics
Phosphopyruvate Hydratase / genetics*,  physiology
Spermatogenesis / genetics*
Spermatozoa / abnormalities*,  enzymology,  ultrastructure
Grant Support
ID/Acronym/Agency:
ES070076/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
EC 4.2.1.11/Phosphopyruvate Hydratase; EC 4.2.1.11/enolase 4 protein, mouse
Comments/Corrections

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