期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1852, 期 5, 页码 1029-1037出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2015.02.007
关键词
Ribosomopathy; Bowen-Conradi syndrome; Intrauterine growth retardation; Proliferation; Mitotic progression; Ribosome biogenesis
资金
- Manitoba Institute of Child Health, Inc.
- Canadian Institutes of Health Research [MOP 62786]
- Canadian Institutes of Health Research
- Manitoba Health Research Council
- Manitoba Institute of Child Health
Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored. (C) 2015 Elsevier B.V. All rights reserved.
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