The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis

RBM and DAZ/SPGY are two families of genes located on the Y chromosome that encode proteins containing RNA-binding motifs, and both have been described as candidate human spermatogenesis genes(1,2). Transmission of deletions from father to son has been observed in the case of DAZ(3-5), but neither gene family has been shown to be essential for spermatogenesis in human males. The DAZ/SPGY genes are particularly amenable to a knockout approach, as they are found on the Y chromosome in Old World primates and apes(6), but in other mammals, they are represented only by an autosomal gene, DAZLA(7-10), which is also present in Old World primates and apes. It has also been shown that a Dazla homologue is essential for spermatogenesis in Drosophila(11). Here we show that Dazla protein is cytoplasmic in male and female germ cells, unlike the nuclear RBM protein(12) Disruption of the Dazla gene leads to loss of germ cells and complete absence of gamete production, demonstrating that Dazla is essential for the differentiation of germ cells.