Gene structure and expression of the mouse dyskeratosis congenita gene, Dkc1

Mutations in the DKC1 gene are responsible for causing X-linked recessive d yskeratosis congenita (DKC) and a more severe allelic variant of the diseas e, Hoyeraal-Hreidarsson syndrome. Both diseases are characterized by progre ssive and fatal bone marrow failure. The nucleolar protein dyskerin is the pseudouridine synthase component of the box H+ACA snoRNAs and also interact s with the RNA component (human telomerase, hTR) of the telomerase complex. Dyskerin is therefore thought to function in the processing of pre-rRNA an d of the hTR, strengthening the notion that the underlying mechanism of DKC is a premature senescence of cells, especially of the rapidly dividing epi thelial and hemopoietic cells. To examine the functions of dyskerin in vivo , it will be necessary to generate mouse models. As a first step, we here p rovide the genomic structure of the mouse Dkc1 gene and expression analysis of the transcript. Northern hybridizations revealed the tissue-specific ex pression of an alternative 4.5-kb transcript, in addition to the ubiquitous 2.6-kb transcript. RNA in situ hybridizations on day 10.5-18.5 postconcept ion embryos showed a ubiquitous expression of Dkc1 with a notably higher le vel of expression confined to the epithelial tissues. In addition, higher l evel Dkc1 expression was confined to embryonic neural tissues as well as to specific neurons in the cerebellum (Purkinje cells) and the olfactory bulb (mitral cells) of the adult brain. In adult testis, elevated expression wa s limited to the Leydig cells. The results indicate that some of the pertin ent functions of dyskerin may be more tissue-specific than previously thoug ht and are not limited to rapidly dividing cells. (C) 2000 Academic Press.