The cause of vertebrate congenital caudal duplication

脊椎动物先天性尾重复的原因

• 批准号: 7137517
• 负责人: Kathleen Joyce Millen
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7137517
• 关键词: clinical research; congenital skeletal disorder; developmental genetics; disease /disorder etiology; embryogenesis; family genetics; gene expression; gene mutation; genetic disorder; genetic mapping; genetic strain; human subject; laboratory mouse; mammalian embryology; mutant; patient oriented research; phenotype

DESCRIPTION (provided by applicant): Congenital caudal duplication, also known as caudal dipygus or parasitic posterior twinning, is a rare birth defect in humans and other vertebrates characterized by supernumerary lower limbs and pelvic structures. The phenotype is striking and presents a number of challenges to current models of vertebrate development. While there have been multiple case reports, there has never been a systematic analysis of the phenomenon, largely because all cases have been sporadic. To date, no heritable vertebrate model has been described for this extraordinary phenotype, and there is no understanding of its developmental basis. Recently a spontaneous mouse mutant arose in the investigator's breeding facility with this remarkable malformation. The trait is heritable as a single, autosomal dominant locus, with incomplete penetrance. There is no evidence that this represents an axial duplication, since the neural tube is not split. Rather, this mouse model appears to be a rare example of a contiguous mirror image segmental duplication of the sacral region, involving all three germ layers. Genetic and embryonic analyses are proposed to map the locus and define the disrupted developmental mechanisms underlying this phenotype, and are certain to provide new and exciting insights regarding vertebrate patterning. Further, an understanding of the nature of the genetic lesion will illuminate the mechanisms underlying variable expression and low penetrance that are characteristic of many birth defects in humans.

描述（由申请人提供）：先天性尾尾复制，也称为尾二二齿或寄生后双胞胎，在人类和其他脊椎动物中是罕见的出生缺陷，其特征是级别的下肢和骨盆结构。 表型令人震惊，并给当前脊椎动物发展模型带来了许多挑战。 尽管有多个病例报告，但从未对该现象进行系统的分析，这主要是因为所有病例都是零星的。 迄今为止，尚无针对这种非凡表型的可遗传脊椎动物模型，并且对其发展基础尚无了解。 最近，在研究人员的育种设施中出现了一种自发的小鼠突变体，并具有明显的畸形。 该特征作为一个单一的常染色体主要基因座，具有不完整的外渗性。 没有证据表明这代表轴向重复，因为神经管没有分裂。 相反，该小鼠模型似乎是s骨区域连续的镜像部分分段重复的一个罕见例子，涉及所有三个细菌层。 提出了遗传和胚胎分析来绘制该表型的基因座并定义破坏的发育机制，并肯定会提供有关脊椎动物图案的新的令人兴奋的见解。 此外，对遗传病变本质的理解将阐明可变表达和低渗透性的机制，这是人类许多先天缺陷的特征。