title: Generation of an iPSC line from a patient with tyrosine hydroxylase (TH) deficiency: TH-1 iPSC.
abstract: Fibroblasts from a male patient with compound heterozygous variants in the tyrosine hydroxylase gene (TH; OMIM: 191290; c.[385-C>T]; [692-G>C]/p.[R129*]; [R231P]), the rate-limiting enzyme for dopamine synthesis, were reprogrammed to iPSCs using episomal reprogramming delivering the reprogramming factors Oct3/4, Sox2, L-Myc, Lin28, Klf4 and p53 shRNA Okita et al. (2011). Pluripotency of TH-1 iPSC was verified by immunohistochemistry and RT-PCR analysis. Cells exhibited a normal karyotype and differentiated spontaneously into the 3 germ layers in vitro. TH-1 iPSC represents the first model system to study the pathomechanism of this rare metabolic disease and provides a useful tool for drug testing.
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: sabine.jung-klawitter@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Jung-Klawitter
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.affiliation: Paul-Ehrlich Institute, Langen, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Sebe
authors.affiliation: Department of Human Genetics, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Ebersold
authors.affiliation: Department of Human Genetics, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D020821:Dystonic Disorders / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006579:Heterozygote; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059785:Karyotype; D000090062:Kruppel-Like Factor 4; D008297:Male; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA; D014446:Tyrosine 3-Monooxygenase