The topographical expression map of chromosome 21 genes.

Down syndrome (DS), caused by the presence of an extra copy of human chromosome 21 (HC21), is the most common genetic cause of mental retardation with an incidence of approximately 1/700 live births. The sequence of the human chromosome 21 provided evidence for the presence of approximately 220 genes. An important challenge is now to understand how three normal copies of these genes are associated with the various DS phenotypes (mental retardation, congenital heart disease, early onset Alzheimers disease and an increased risk of leukemia). To define where HC21 genes exert their function and identify their possible role in the DS phenotype we have decided to perform a systematic analysis of the expression profile of their murine homologues . We collected 150 murine cDNA clones from several sources. To obtain a high resolution expression pattern several complementary methods were combined: (i) RT-PCR on a mouse cDNA panel of 12 adult tissues and 4 developmental stages; (ii) wholemount in situ hybridisation of E9.5 and E10.5 embryos and (iii) section in situhybridisation of E14.5 embryos and of P7 brains. This set of whole embryos and sections corresponds to mid and late embryonic and foetal human periods, when most of the major organs and body regions are organised. Genes showing an interesting and/or restricted expression pattern were analysed further on appropriate sections at more developmental timepoints. 87% of the tested genes showed a clear expression pattern during murine development. In 37% of the cases expression was ubiquitous while 50% of the cDNAs showed a differential expression pattern in the embryonal tissues. The topographical catalogue of expression of the murine homologues of human chromosome 21 genes will be instrumental to the understanding of the pathogenesis of trisomy 21. Currently, approximately 100 genes have already been tested some of which display a pattern of expression relevant to the congenital heart disease and to the mental retardation observed in DS. The entire data set will be made available to the scientific community via a web site.