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MMACHC Regulates Craniofacial Development

MMACHC 调节颅面发育

基本信息

批准号：
10322429
负责人：
Anita M Quintana
金额：
$ 15.1万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10322429
关键词：
Alcian Blue Animals Binding Biological Models CRISPR/Cas technology Cartilage Cell Differentiation process Cobalamin Congenital Abnormality Craniofacial Abnormalities Data Defect Development Developmental Gene Disease Embryo Enzymes Event Face Fertilization Future Genes Genetic Hereditary Disease Homocysteine Hour Human Inborn Errors of Metabolism Individual Larva Live Birth Metabolic Metabolism Methylmalonic Acid Modeling Molecular Multipotent Stem Cells Mus Mutation Neck Neural Crest Cell Patients Phenotype Positioning Attribute Prevalence Production Reaction Reporting Stains Syndrome Testing Time Toxic effect Variant Vitamin B 12 Zebrafish base bone congenital anomaly cost effective craniofacial craniofacial development experimental study gene function genome editing knock-down loss of function methylmalonic aciduria mouse development mutant preimplantation prevent restoration stem cells

项目摘要

cblC is a multiple congenital anomaly syndrome caused by mutations in the MMACHC gene. cblC is characterized by defects in cobalamin (vitamin B12) metabolism, but mild to moderate craniofacial abnormalities have been consistently documented in patients. Mutations in the mouse Mmachc gene are developmentally lethal and therefore, the mechanisms underlying the craniofacial deficits associated with cblC are not completely understood. Here we seek to produce a viable zebrafish model of cblC syndrome with which to understand the function of MMACHC in facial development. Specifically, we will determine whether the facial anomalies present in cblC are associated with the accumulation of toxic metabolites and cobalamin binding. Our studies have the potential to reveal a potentially paradigm shifting function for MMACHC in facial development and will help to prevent and treat metabolically associated craniofacial phenotypes.

cblC 是一种由 MMACHC 基因突变引起的多发性先天异常综合征。 cblC 是其特征是钴胺素（维生素 B12）代谢缺陷，但有轻度至中度颅面异常已在患者中得到一致记录。小鼠 Mmachc 基因突变对发育有影响致命的，因此，与 cblC 相关的颅面缺陷的潜在机制尚不完全清楚。明白了。在这里，我们寻求建立一个可行的 cblC 综合征斑马鱼模型，以了解 MMACHC 在面部发育中的功能。具体来说，我们将确定面部是否存在异常 cblC 中的 CBLC 与有毒代谢物的积累和钴胺素结合有关。我们的研究有有可能揭示 MMACHC 在面部发育中潜在的范式转变功能，并将有助于预防和治疗代谢相关的颅面表型。