Nature 386, 713 - 717 (17 April 1997); doi:10.1038/386713a0

Arrest of spermatogenesis and defective breast development in mice lacking A-myb

Antonio Toscani^*, Richard V. Mettus^*, Robert Coupland^†, Henry Simpkins^*†, Judith Litvin^*‡, Joanne Orth^‡, Kimi S. Hatton^*§ & E. Premkumar Reddy^*§

^* Fels Institute for Cancer Research and Molecular Biology, Departments of ^§ Biochemistry, ^† Pathology, ^‡ Anatomy and Cell Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, Pennsylvania 19140, USA
These authors contributed equally to this work.

The Myb gene family currently consists of three members, named A-, B- and c-myb ^1,2. These genes encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In adult male mice, A-myb is expressed predominantly in male germ cells^2,3. In female mice, A-myb is expressed in breast ductal epithelium, mainly during pregnancy-induced ductal branching and alveolar development. We report here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis. Morphological examination of the testes of A-myb ^-/- males revealed that the germ cells enter meiotic prophase and arrest at pachytene. In adult homozygous null A-myb female mice, the breast epithelial compartment showed underdevelopment of breast tissue following pregnancy and the female mice were unable to nurse their newborn pups. These results demonstrate that A-myb plays a critical role in spermatogenesis and mammary gland development.

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