PubMed · 8581649
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M Tsuda. 1995. [Chromosomal abnormalities].. https://pubmed.ncbi.nlm.nih.gov/8581649/
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PURPOSE: Alagille syndrome (ALGS) is an autosomal dominantly inherited disorder primarily caused by mutations in the Jagged Canonical Notch Ligand 1 (JAG1) gene. Although many pluripotent stem cells are well established, no patient-derived stem cells from exfoliated deciduous teeth (SHED) have been developed. In this study, we aimed to establish SHED from an ALGS patient carrying a heterozygous JAG1mut mutation. METHODS: We isolated SHED from a deciduous tooth of an ALGS patient with a heterozygous JAG1 mutation (ALGS-SHED) by the colony-forming unit-fibroblast (CFU-F) method. We then compared the characteristics of ALGS-SHED and healthy donor-derived control SHED (CONT-SHED). RESULTS: ALGS-SHED displayed mesenchymal stem cell features as indicated by CFU-F formation, immunophenotype, and mesenchymal multipotency into adipocytes, chondrocytes, and osteoblasts. ALGS-SHED showed reduced population doubling capacity and exhibited induced chondrogenic potency and diminished osteogenic potency, but similar hepatic potency. ALGS-SHED damaged in situ potency to form bile duct-like tubular structures in the livers of chronically CCl4-injured mice. CONCLUSIONS: We successfully established ALGS-SHED from an ALGS patient carrying a heterozygous JAG1 mutation. Our established ALGS-SHED may represent a potential model for studying ALGS involving a JAG1 mutation.
We describe a patient with Hirschsprung disease and autism. High-resolution karyotyping indicated that the patient has an interstitial deletion of 20p11.22-p11.23. Microsatellite analysis showed a deletion involving a 5-6 cM region from the maternally derived chromosome 20. The deleted region is proximal to, and does not overlap, the recently characterized Alagille syndrome region. This region of 20p has not yet been implicated in Hirschsprung disease or autism. However, this region contains several genes that could plausibly contribute to any phenotype that includes abnormal neural development.
Notch proteins are a family of closely related transmembrane receptors proven to be instrumental in cell fate decisions. Recently, Notch ligands Delta and Jagged have been identified in Drosophila and rat, respectively. We have isolated the human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP-D20S186-cen). Alagille syndrome is an autosomal dominant disorder characterized by neonatal jaundice, paucity of intrahepatic bile ducts, and abnormalities of the heart, skeleton, and eyes. The human Jagged1 (JAG1), therefore, appears to be a strong candidate gene for this disease. Here we describe the identification, full-length cDNA cloning, expression patterns, and precise physical location of this gene within the Alagille syndrome critical region.