Absence of mDazl produces a final block on germ cell development at meiosis

Reproduction - Tập 126 Số 5 - Trang 589-597 - 2003
Philippa Saunders1, Justine Turner2, Matteo Ruggiu3, Mary Taggart3, Paul S. Burgoyne2, David J. Elliott4, Howard J. Cooke3
1Medical Research Council Human Reproductive Sciences Unit, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
2Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
3Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK; and
4University of Newcastle, Institute for Human Genetics, International Centre for Life, Central Parkway, Newcastle Upon Tyne, NE1 3BZ, UK

Tóm tắt

The autosomal gene DAZL is a member of a family of genes (DAZL, DAZ, BOULE), all of which contain a consensus RNA binding domain and are expressed in germ cells. Adult male and female mice null for Dazl lack gametes. In order to define more precisely the developmental stages in germ cells that require Dazl expression, the patterns of germ cell loss in immature male and female wild-type (+/+, WT) and Dazl -/- (DazlKO) mice were analysed. In females, loss of germ cells occurred during fetal life and was coincident with progression of cells through meiotic prophase. In males, testes were recovered from WT and DazlKO males obtained before and during the first wave of spermatogenesis (days 2-19). Mitotically active germ cells were present up to and including day 19. Functional differentiation of spermatogonia associated with detection of c-kit positive cells did not depend upon expression of Dazl. RBMY-positive cells (A, intermediate, B spermatogonia, zygotene and preleptotene spermatocytes) were reduced in DazlKO compared with WT testes. Staining of cell squashes from day 19 testes with anti-gamma-H2AX and anti-SCP3 antibodies showed that germ cells from DazlKO males were unable to progress beyond the leptotene stage of meiotic prophase I. It was concluded that in the absence of Dazl, germ cells can complete mitosis, and embark on functional differentiation but that, in both sexes, progression through meiotic prophase requires this RNA binding protein.

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Reproduction

Tập 126 Số 5

589-597

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