Open AccessLoss of the Mouse Ortholog of the Shwachman-Diamond Syndrome Gene (Sbds) Results in Early Embryonic Lethality
Author(s) -
Siyi Zhang,
Mingjun Shi,
Chichung Hui,
Johanna M. Rommens
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00091-06
Subject(s) - biology , phenotype , embryonic stem cell , gene , genetics , loss function , mutation , cancer research , microbiology and biotechnology
Mutations inSBDS are responsible for Shwachman-Diamond syndrome (SDS), a disorder with clinical features of exocrine pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. SBDS is a highly conserved protein whose function remains largely unknown. We identified and investigated the expression pattern of the murine ortholog. Variation in levels was observed, but Sbds was found to be expressed in all embryonic stages and most adult tissues. Higher expression levels were associated with rapid proliferation. A targeted disruption ofSbds was generated in order to understand the consequences of its loss in an in vivo model. Consistent with recessive disease inheritance for SDS,Sbds +/− mice have normal phenotypes, indistinguishable from those of their wild-type littermates. However, the development ofSbds −/− embryos arrests prior to embryonic day 6.5, with muted epiblast formation leading to early lethality. This finding is consistent with the absence of patients who are homozygous for early truncating mutations.Sbds is an essential gene for early mammalian development, with an expression pattern consistent with a critical role in cell proliferation.