title: Lymphoid-specific helicase (HELLS) is essential for meiotic progression in mouse spermatocytes.
abstract: Lymphoid-specific helicase (HELLS; also known as LSH) is a member of the SNF2 family of chromatin remodeling proteins. Because Hells-null mice die at birth, a phenotype in male meiosis cannot be studied in these animals. Allografting of testis tissue from Hells(-/-) to wild-type mice was employed to study postnatal germ cell differentiation. Testes harvested at Day 18.5 of gestation from Hells(-/-), Hells(+/-), and Hells(+/+) mice were grafted ectopically to immunodeficient mice. Bromodeoxyuridine incorporation at 1 wk postgrafting revealed fewer dividing germ cells in grafts from Hells(-/-) than from Hells(+/+) mice. Whereas spermatogenesis proceeded through meiosis with round spermatids in grafts from Hells heterozygote and wild-type donor testes, spermatogenesis arrested at stage IV, and midpachytene spermatocytes were the most advanced germ cell type in grafts from Hells(-/-) mice at 4, 6, and 8 wk after grafting. Analysis of meiotic configurations at 22 days posttransplantation revealed an increase in Hells(-/-) spermatocytes with abnormal chromosome synapsis. These results indicate that in the absence of HELLS, proliferation of spermatogonia is reduced and germ cell differentiation arrested at the midpachytene stage, implicating an essential role for HELLS during male meiosis. This study highlights the utility of testis tissue grafting to study spermatogenesis in animal models that cannot reach sexual maturity.
authors.affiliation: Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, USA.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Zeng
authors.forename: Claudia
authors.initials: C
authors.lastname: Baumann
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidtmann
authors.forename: Ali
authors.initials: A
authors.lastname: Honaramooz
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Alla
authors.initials: A
authors.lastname: Bondareva
authors.forename: Camila
authors.initials: C
authors.lastname: Dores
authors.forename: Tao
authors.initials: T
authors.lastname: Fan
authors.forename: Sichuan
authors.initials: S
authors.lastname: Xi
authors.forename: Theresa
authors.initials: T
authors.lastname: Geiman
authors.forename: Rahul
authors.initials: R
authors.lastname: Rathi
authors.forename: Dirk
authors.initials: D
authors.lastname: de Rooij
authors.forename: Rabindranath
authors.initials: R
authors.lastname: De La Fuente
authors.forename: Kathrin
authors.initials: K
authors.lastname: Muegge
authors.forename: Ina
authors.initials: I
authors.lastname: Dobrinski
mesh_terms: D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D008540:Meiosis; D051379:Mice; D013090:Spermatocytes / Q000166:cytology* / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology
chemical_list: D004265:DNA Helicases; C487055:Hells protein, mouse