International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 82 - USING SEGMENTALLY TRISOMIC MICE TO DETERMINE THE MECHANISM OF GENE ACTION RESPONSIBLE FOR DOWN SYNDROME CEREBELLAR PHENOTYPES

Ms. Lisa Olson
Johns Hopkins University School of Medicine
725 N. Wolfe St.
Biophysics 203
Baltimore, MD 21205
USA
410-955-6624 (phone)
410-614-8731 (fax)

Co-Authors: 1) Olson LE, 1) Baxter LL, 2) Carlson EJ, 2) Epstein CJ, 1) Reeves RH
Institutions: 1) Johns Hopkins University School of Medicine, Baltimore, MD  2) University of California at San Francisco. 

In rare individuals with chromosomal translocations, Down syndrome (DS) is caused by partial trisomy of chromosome (Chr) 21.  Correlation of the smallest regions of overlap in such individuals also displaying the same characteristics of DS has led to the hypothesis that many aspects of the phenotype arise from dosage imbalance of one or a few genes.  An alternative hypothesis asserts that DS phenotypes result from small effects of hundreds of genes at dosage imbalance.  Segmentally trisomic mice, which produce dosage imbalance for different numbers of Chr 21 gene orthologs, provide sensitive models in which to test this hypothesis.

By comparing mouse Chr 16 and human Chr 21, we know that Ts1Cje and Ts65Dn mice are respectively trisomic for 85 and 124 of the 225 catalogued Chr 21 genes.  Ts65Dn mice, like individuals with DS, have reduced volume and cellular density in the cerebellum (Baxter et al., 2000); thus, trisomy for roughly half of the genes on Chr 21 is sufficient to produce this DS phenotype.  The cerebellum of the Ts1Cje mouse is affected more mildly than that of the Ts65Dn mouse.  Although cerebellar volume is reduced to the same extent as Ts65Dn mice (88% of euploid), granule cell density is substantially less affected in Ts1Cje (90% of euploid) as compared to Ts65Dn (76%).  The Ts1Cje mice did not show the reduced Purkinje cell density found in Ts65Dn.  This graded severity of the cerebellar phenotype with decreasing amounts of trisomy supports the hypothesis that multiple genes contribute to this phenotype of DS.

Baxter, L. L., T. H. Moran, J. T. Richtsmeier, J. Troncoso, and R. H. Reeves.  2000.  Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse.  Hum Mol Genet 9: 195-202.


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

Base url http://imgs.org
Last modified: Saturday, November 3, 2012