International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


GENOTYPE: PHENOTYPE CORRELATIONS IN MOUSE MODESL ILLUMINATE MOLECULAR MECHANISMS OF DOWN SYNDROME

Roger Reeves
Johns Hopkins University Schl. Med.
Dept. of Physiology
Baltimore MD 21205 USA

Co-Authors: 1&2)Richtsmeier J, 3)Zumwalt A, 4)Carlson E, 4)Epstein C, 5)Reeves R
Institutions: 1)Dept of Anthropology, The Pennsylvania State University, 2)Centre for Craniofacial Development and Disorders, The Johns Hopkins Hospital, 3)Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, 4)Dept of Pediatrics, University of California, 5)Department of Physiology, Johns Hopkins University School of Medicine

Trisomy for chromosome 21 (Chr 21) is the most complex genetic disorder compatible with human survival. It has profound effects on development that result in a constellation of phenotypes known as Down syndrome (DS). Distinctive craniofacial dysmorphology is among the few features common to all individuals with DS. The characteristic DS facies result primarily from maldevelopment of the underlying craniofacial skeleton and mandible. The Ts65Dn mouse, which has segmental trisomy 16 producing dosage imbalance for about half the genes found on human Chr 21, exhibits specific skeletal deformations corresponding directly to the craniofacial dysmorphogenesis in DS (Richtsmeier et al., 2000). Here we demonstrate that Ts1Cje mice, which are at dosage imbalance for about 70% of the genes triplicated in Ts65Dn, demonstrate a very similar pattern of anomalies in the craniofacial skeleton. However, one character of Ts65Dn mice, a broadening of the cranial vault contributing to brachycephaly, is not seen in Ts1Cje mice. These observations independently confirm that dosage imbalance for mouse genes orthologous to those on human Chr 21 has corresponding effects in both species. The subtle differences in the craniofacial phenotypes of Ts1Cje and Ts65Dn mice have implications for elucidation of the mechanisms by which this aneuploidy disrupts development.


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