Non-Syndromic Cleft Palate in Mice

小鼠非综合征性腭裂

• 批准号: 6967138
• 负责人: ERIC T. EVERETT
• 金额: $ 11.23万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967138
• 关键词: animal genetic material tag; autosomal recessive trait; biotechnology; cleft palate; computer assisted sequence analysis; developmental disease /disorder; developmental genetics; gene environment interaction; gene expression; gene mutation; genetic library; genetic regulation; genetic screening; genetic susceptibility; genetically modified animals; in situ hybridization; laboratory mouse; linkage mapping; molecular cloning; molecular pathology; nucleic acid sequence; pathologic process; polymerase chain reaction

DESCRIPTION (provided by applicant): Development of the mammalian secondary palate is a complex and critical process that in man can be easily perturbed leading to the common and distressing birth defect, cleft palate (CP). Clefts of the primary and/or secondary palates are consistently included among the more common congenital anomalies occurring in man. Even though the combination of cleft lip with/or without cleft palate (CLIP) is more commonly seen, isolated CP can account for approximately one-third of the documented cases. Isolated CP is considered to be an etiologically heterogeneous trait with an important genetic contribution. While CP can be associated with more that 350 characterized disorders, more than 50% of cases of CP occur as isolated (sporadic) and thought to be free of other anomalies (non-syndromic). Our long-term objectives focus on identifying genetic determinants that directly and/or indirectly (i.e. genetic susceptibility and multifactorial causes) contribute to the failure of mammalian secondary palate formation (using animal models) and to better understand the roles that these genes play at the molecular level during normal secondary palate formation. Similarities in palate development between humans and mice have allowed the later to be an important model organism for studying normal and defective palatogenesis. Transgene insertion mutagenesis can facilitate the identification of developmentally important genes through non-homologous disruption of endogenous genes. We have been investigating four separate lines of transgenic mice that develop autosomal recessive nonsyndromic cleft palate involving a least three distinct loci that localize to chromosomes 3 and 4. The focus of this research project is to characterize the interval of genomic DNA disrupted by these transgene insertions as a prelude to identifying the disrupted genes responsible for cleft palate in these mice.

描述（由申请人提供）：哺乳动物次要味觉的发展是一个复杂而关键的过程，在人中很容易受到扰动，导致常见和令人痛苦的先天缺陷，cleft裂（CP）。在人类发生的更常见的先天性异常中，原发性和/或次要口感的裂口一直包括在内。即使更常见的是/或没有裂口（剪辑）的裂口与/或没有裂口的组合，但孤立的CP也可以占据记录的病例的三分之一。分离的CP被认为是具有重要遗传贡献的病因异质性状。尽管CP可以与350个特征性疾病相关联，但超过50％的CP病例以孤立（零星）的形式出现，并被认为不含其他异常（非综合症）。我们的长期目标着重于识别直接和/或间接（即遗传易感性和多因素原因）的遗传决定因素，这有助于哺乳动物次生味的形成（使用动物模型）的失败，并更好地了解这些基因在正常二次乳酸形成下在分子水平上起着的作用。人类和小鼠之间的口感发育的相似性已使后来成为研究正常和有缺陷的古质发生的重要模型生物。转基因插入诱变可以通过内源基因的非同源破坏来促进发育重要基因的鉴定。 We have been investigating four separate lines of transgenic mice that develop autosomal recessive nonsyndromic cleft palate involving a least three distinct loci that localize to chromosomes 3 and 4. The focus of this research project is to characterize the interval of genomic DNA disrupted by these transgene insertions as a prelude to identifying the disrupted genes responsible for cleft palate in these mice.