Lmbrd1 expression is essential for the initiation of gastrulation

Buers I., Pennekamp P., Nitschke Y., Lowe C., Skryabin B., Rutsch F.

Research article (journal) | Peer reviewed

Abstract

The rare inborn cblF defect of cobalamin metabolism is caused by mutations in the limb region 1 (LMBR1) domain containing 1 gene (LMBRD1). This defect is characterized by massive accumulation of free cobalamin in lysosomes and loss of mitochondrial succinyl-CoA synthesis and cytosolic methionine synthesis. Affected children suffer from heart defects, developmental delay and megaloblastic anemia. LMBRD1 encodes for LMBD1, a predicted lysosomal cobalamin transport protein. In this study, we determine the physiological function of LMBRD1 during embryogenesis by generating Lmbrd1 deficient mice using the Cre/LoxP system. Complete loss of Lmbrd1 function is accompanied by early embryonic death in mice. Whole mount in situ hybridization studies against bone morphogenetic protein 4 and Nodal show that initial formation of the proximal–distal axis is unaffected in early embryonic stages whereas the initiation of gastrulation is disturbed shown by the expression pattern of even skipped homeotic gene 1 and fibroblast growth factor 8 in Lmbrd1 deficient mice. We conclude that intact function of LMBD1 is essential for the initiation of gastrulation.

Details about the publication

JournalJournal of Cellular and Molecular Medicine (J Cell Mol Med)
Volume20
Issue8
Page range1523-1533
StatusPublished
Release year2016
Language in which the publication is writtenEnglish
DOI10.1111/jcmm.12844
Link to the full texthttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84979059282&origin=inward
Keywordscobalamin metabolism; embryonic development; gastrulation; Lmbrd1−/−-embryos

Authors from the University of Münster

Pennekamp, Petra
Institute of Human Genetics
Skryabin, Boris
Centre for Molecular Biology of Inflammation