MMACHC Regulates Craniofacial Development

MMACHC 调节颅面发育

• 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
• 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

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是由MMACHC基因突变引起的多个先天性异常综合征。 CBLC是 以钴胺素缺陷（维生素B12）代谢为特征，但轻度至中度颅面异常 在患者中一直记录在患者中。小鼠MMACHC基因中的突变在发育上是 致命，因此，与CBLC相关的颅面缺陷的基础机制并非完全 理解。在这里，我们试图产生可行的CBLC综合征模型，以了解该模型 MMACHC在面部发育中的功能。具体而言，我们将确定面部异常是否存在 在CBLC中，有毒代谢产物和钴胺素结合的积累有关。我们的研究有 有可能在面部发育中揭示MMACHC的潜在范式转移功能，并将有助于 预防和治疗代谢相关的颅面表型。