Finding the cause of vertebrate congenital caudal duplication

University Of Chicago, Chicago IL

Investigators

Linked publications & trials

Abstract

[unreadable] 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. [unreadable] [unreadable] [unreadable]