Down syndrome is a major cause of mental retardation and congenital heart defects. While most of the affected individuals have three copies of chromo some 21, patients with partial trisomy 21 have also been described. These rare cases define a minimal region for the Down syndrome phenotype encompassing about 3 Mb around D21S55. By using a new method for the identification of coding sequences (Alu-splice PCR) we have identified a new gene, DSCR1, from region 21q22.1–q22.2. DSCR1 encodes a novel protein which has an acidic domain, a serine-proline motif, a putative DNA binding domain and a proline-rich region with the characteristics of a SH3 domain ligand. These features suggest that DSCR1 could be involved in transcriptional regulation and/or signal transduction. DSCR1 is highly expressed in human brain and heart, and increased expression in the brains of young rats compared with adults suggests a role for DSCR1 during central nervous system development. Structural characteristics, together with its particular expression in brain and heart, encourage us to suggest that the overexpression of DSCR1 may be involved in the pathogenesis of Down syndrome, in particular mental retardation and/ or cardiac defects.

Gene transfer vectors derived from human immunodeficiency virus (HIV-1) efficiently transduce nondividing cells and remain stably integrated in their genome. Long-term expression of reporter genes has been documented after intracerebral injection of these vectors. Using a HIV-based vector, we looked for a reversal of brain damage in the β-glucuronidase-deficient mucopolysaccharidosis type VII mouse, an animal model of human lysosomal storage diseases. The vector suspension was injected stereotactically in the brain of 10-weekold animals, an age at which storage lesions are patent in glia, perivascular cells, and neurons. Either a single intrastriatal injection or multiple injections in both cerebral hemispheres and in the cerebellum were performed. Local tolerance, enzyme delivery, and correction of storage lesions were investigated by comprehensive analysis of serial sections of the entire brain of mice killed 6 or 16 weeks postinjection. Histochemical staining detected enzyme activity in widely distributed areas, the size of which increased with time. Clearance of lysosomal storage extended far beyond enzyme-positive areas. In mice receiving multiple injections of the vector, complete correction or significant reduction of the pathology was observed in every section, suggesting disease regression in the entire brain. These results may have implications for the treatment of neurological symptoms in lysosomal storage diseases.

Mt is a cross-disciplinary biomedical journal devoted to publishing the most exciting advances in pharmacology and therapeutics, as they pertain to advances in translational and clinical medicine. It is recognized as one of the most prestigious journals in the field. With an impact factor of 6.825*, mt ranks in the top 4.2% of scientific journals in the latest Science Citation Index. Published monthly online and in print.

Mt is a cross-disciplinary biomedical journal devoted to publishing the most exciting advances in pharmacology and therapeutics, as they pertain to advances in translational and clinical medicine. It is recognized as one of the most prestigious journals in the field. With an impact factor of 6.825*, mt ranks in the top 4.2% of scientific journals in the latest Science Citation Index. Published monthly online and in print.