Lahoud M H, Ristevski S, Venter D J, Jermiin L S, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog P J, Kola I
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
Genome Res. 2001 Aug;11(8):1327-34. doi: 10.1101/gr.168801.
We have cloned and characterized a novel murine DNA-binding protein Desrt, with a motif characteristic of the ARID (A-T rich interaction domain) family of transcription factors. The Desrt gene encodes an 83-kD protein that is shown to bind DNA and is widely expressed in adult tissues. To examine the in vivo function of Desrt, we have generated mice with a targeted mutation in the ARID domain of Desrt. Homozygous mutants have reduced viability, pronounced growth retardation, and a high incidence of abnormalities of the female and male reproductive organs including cryptorchidism. This may thus serve as a model to dissect the mechanisms involved in the development of the reproductive tract including testicular descent. Gene-targeted mice also display a reduction in the thickness of the zona reticularis of the adrenal gland and transient aberrations of the T and B cell compartments of primary lymphoid organs. These data show that this novel DNA-binding protein, Desrt, has a nonredundant function during growth and in the development of the reproductive system.
我们克隆并鉴定了一种新型小鼠DNA结合蛋白Desrt，它具有转录因子ARID（富含A-T相互作用结构域）家族的特征基序。Desrt基因编码一种83-kD的蛋白质，该蛋白质可与DNA结合，并在成年组织中广泛表达。为了研究Desrt在体内的功能，我们构建了在Desrt的ARID结构域中有靶向突变的小鼠。纯合突变体的活力降低，生长明显迟缓，雌性和雄性生殖器官出现异常的发生率很高，包括隐睾症。因此，这可以作为一个模型来剖析参与生殖道发育（包括睾丸下降）的机制。基因靶向小鼠还表现出肾上腺网状带厚度的减少以及初级淋巴器官中T和B细胞区室的短暂异常。这些数据表明，这种新型DNA结合蛋白Desrt在生长和生殖系统发育过程中具有非冗余功能。
