Latham K E, Litvin J, Orth J M, Patel B, Mettus R, Reddy E P
The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Oncogene. 1996 Sep 19;13(6):1161-8.
We recently reported the cloning and sequencing of the mouse A-myb proto-oncogene cDNA and the abundant expression of this mRNA primarily in the testis of adult mice. The A-myb mRNA is detectable by in situ hybridization specifically in the spermatogenic cells, and is downregulated during terminal differentiation. A low level of expression is observed in a few other tissues, including ovary, spleen and brain. We have extended those studies by examining A-myb and B-myb expression during testis development in the mouse. The A-myb and B-myb genes are both expressed in a cell- and stage-specific manner during testis development. The B-myb mRNA is expressed most highly in gonocytes of the fetal testis and in spermatogonia and early spermatocytes in the adult. B-myb expression decreases at day 18 post partum, coincident with the initial appearance of late pachytene spermatocytes. B-myb expression was also detectable in some interstitial cells of the fetal and adult testis. The A-myb mRNA was not detectable by in situ hybridization in fetal day 15.5 gonocytes but was detectable at a low abundance by RT-PCR in fetal and newborn mice. A-myb mRNA expression increased at post-natal day 10, when primary spermatocytes first appear. In the adult, the A-myb mRNA was expressed highly in a sub-population of spermatogonia and in primary spermatocytes, but was not detectable in spermatids. This expression of A-myb is consistent with the meiotic arrest that is observed in A-myb-deficient male mice. We conclude that B-myb may play a critical role in controlling the proliferation or differentiation of gonocytes and spermatogonia and possibly the somatic lineages as well, whereas A-myb is required for progression through the first meiotic prophase. These distinct roles for B-myb and A-myb during spermatogenesis may reflect distinct transactivation potentials of the two proteins. Further studies to determine the functions of A-myb and B-myb in the developing testis should improve our understanding of the molecular events associated with spermatogenesis and differentiation of the Sertoli and other somatic cell types of the testis.
我们最近报道了小鼠A-myb原癌基因cDNA的克隆与测序，以及该mRNA主要在成年小鼠睾丸中的大量表达。通过原位杂交可在生精细胞中特异性检测到A-myb mRNA，且在终末分化过程中其表达下调。在包括卵巢、脾脏和大脑在内的其他一些组织中观察到低水平的表达。我们通过研究小鼠睾丸发育过程中A-myb和B-myb的表达扩展了这些研究。在睾丸发育过程中，A-myb和B-myb基因均以细胞和阶段特异性方式表达。B-myb mRNA在胎儿睾丸的生殖母细胞以及成年小鼠的精原细胞和早期精母细胞中表达最高。产后第18天B-myb表达下降，这与晚期粗线期精母细胞的最初出现一致。在胎儿和成年睾丸的一些间质细胞中也可检测到B-myb表达。在胚胎第15.5天的生殖母细胞中，通过原位杂交未检测到A-myb mRNA，但在胎儿和新生小鼠中通过RT-PCR可检测到低丰度表达。出生后第10天，当初级精母细胞首次出现时，A-myb mRNA表达增加。在成年小鼠中，A-myb mRNA在精原细胞亚群和初级精母细胞中高表达，但在精子细胞中未检测到。A-myb的这种表达与在A-myb缺陷雄性小鼠中观察到的减数分裂停滞一致。我们得出结论，B-myb可能在控制生殖母细胞和精原细胞的增殖或分化以及可能的体细胞谱系中起关键作用，而A-myb是减数第一次分裂前期进程所必需的。B-myb和A-myb在精子发生过程中的这些不同作用可能反映了这两种蛋白质不同的反式激活潜能。进一步研究确定A-myb和B-myb在发育中的睾丸中的功能，应能增进我们对与精子发生以及睾丸支持细胞和其他体细胞类型分化相关的分子事件的理解。
