International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Roper R J
Johns Hopkins University School of Medicine

Co-Authors: South S T, Reeves R H
Institutions: Johns Hopkins University School of Medicine

Abstract Down syndrome (DS, trisomy 21) is the most frequent human aneuploidy compatible with survival. Neural crest cells (NCC) contribute prominently to many of the structures affected in DS, including craniofacial, heart, and peripheral nervous system, and it has been hypothesized that trisomy 21 causes a defect in NCC. Although widely accepted due to circumstantial evidence, no direct experiments have proven or disproven an effect on NCC in DS. Conceivably, any parameter of NCC generation, migration, signaling or differentiation could be affected by trisomy. The Ts65Dn mouse is at dosage imbalance for orthologs of about half of the genes on human Chr 21 and provides a genetic model with direct parallels in phenotypes and etiology of DS. By generating Ts65Dn mice with a reporter gene specifically labeling cranial NCC during early development, we can visualize and quantify the number of NCC and volume occupied by structures containing NCC. Ts65Dn mice were bred to mice homozygous for the Wnt1-lacZ transgene, and the offspring were dissected from Ts65Dn mothers at embryonic day 9.5. Trisomic and euploid embryos were identified by FISH analysis of the embryonic yolk sac and classified by somite number. Using unbiased stereology, we quantified lacZ-labeled NCC number in pharyngeal arches and pharyngeal arch volume in E9.5 mice. Analysis of this data at somite-specific developmental stages provides a direct experimental test of the effects of trisomy on NCC. The quantitative measure of NCC and structures derived from NCC will also establish a baseline for other analyses of genetic effects on NCC.

Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url
Last modified: Saturday, November 3, 2012