The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice

被引:47
作者
Rainey, Mark A. [1 ]
George, Manju [1 ]
Ying, GuoGuang [2 ]
Akakura, Reiko [3 ]
Burgess, Daniel J. [4 ]
Siefker, Ed [4 ]
Bargar, Tom [5 ]
Doglio, Lynn [6 ]
Crawford, Susan E. [7 ]
Todd, Gordon L. [5 ]
Govindarajan, Venkatesh [4 ]
Hess, Rex A. [8 ]
Band, Vimla [1 ,5 ]
Naramura, Mayumi [1 ]
Band, Hamid [1 ,5 ,9 ]
机构
[1] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Eppley Canc Ctr, Omaha, NE 68198 USA
[2] Tianjin Med Univ, Canc Inst & Hosp, Mol Oncol Lab, Tianjin, Peoples R China
[3] UMDNJ, Dept Biochem & Mol Biol, New Jersey Med Sch, Newark, NJ USA
[4] Creighton Univ, Dept Surg, Omaha, NE 68178 USA
[5] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Coll Med, Omaha, NE USA
[6] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA
[7] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA
[8] Univ Illinois, Dept Vet Biosci, Urbana, IL USA
[9] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Coll Med, Omaha, NE USA
关键词
BLOOD-TESTIS BARRIER; MALE CONTRACEPTIVE DEVELOPMENT; EARLY ENDOSOMAL TRANSPORT; PLASMA-MEMBRANE; SEMINIFEROUS EPITHELIUM; MAMMALIAN-CELLS; KNOCKOUT MICE; C-ELEGANS; PROTEIN; DOMAIN;
D O I
10.1186/1471-213X-10-37
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The C-terminal Eps15 homology domain-containing protein 1 (EHD1) is ubiquitously expressed and regulates the endocytic trafficking and recycling of membrane components and several transmembrane receptors. To elucidate the function of EHD1 in mammalian development, we generated Ehd1(-/-) mice using a Cre/loxP system. Results: Both male and female Ehd1(-/-) mice survived at sub-Mendelian ratios. A proportion of Ehd1(-/-) mice were viable and showed smaller size at birth, which continued into adulthood. Ehd1(-/-) adult males were infertile and displayed decreased testis size, whereas Ehd1(-/-) females were fertile. In situ hybridization and immunohistochemistry of developing wildtype mouse testes revealed EHD1 expression in most cells of the seminiferous epithelia. Histopathology revealed abnormal spermatogenesis in the seminiferous tubules and the absence of mature spermatozoa in the epididymides of Ehd1(-/-) males. Seminiferous tubules showed disruption of the normal spermatogenic cycle with abnormal acrosomal development on round spermatids, clumping of acrosomes, misaligned spermatids and the absence of normal elongated spermatids in Ehd1(-/-) males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in Ehd1(-/-) mice. Conclusions: Contrary to a previous report, these results demonstrate an important role for EHD1 in pre- and postnatal development with a specific role in spermatogenesis.
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页数:19
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