title: Derivation of human embryonic stem cells with NEMO deficiency.
abstract: Deficiency of the nuclear factor-kappa-B essential modulator (NEMO) is a rare X-linked disorder that presents in boys as hypohydrotic ectodermal dysplasia with immunodeficiency due to defective nuclear factor-κB activation. Here we report on the generation of 2 human embryonic stem cell lines from discarded in vitro fertilization (IVF) embryos ascertained via preimplantation genetic diagnosis. We have derived two human embryonic stem cell lines that carry a T458G hypomorphic mutation in exon 4 of the NEMO (or IKBKG) gene. One of the lines is diploid male; the other is diploid female but has clonally inactivated the X-chromosome that harbors the wild-type IKBKG gene. We show that both lines are pluripotent, have the capacity to differentiate into hematopoietic progenitors, and have defective inhibitor of nuclear factor kappa-B kinase activity. These NEMO deficiency hES cell lines provide an unlimited source for differentiated cell types and may serve as a unique tool to study NEMO deficiency and potentially lead to the development of new therapies for this disease.
authors.affiliation: Department of Newborn Medicine and Department of Medicine, Division of Genetics, Brigham & Women's Hospital, Boston, MA, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Guan
authors.forename: Akiko
authors.initials: A
authors.lastname: Yabuuchi
authors.forename: Hongguang
authors.initials: H
authors.lastname: Huo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ginsberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Racowsky
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Paul H
authors.initials: PH
authors.lastname: Lerou
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D041321:Chromosomes, Human, X / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005091:Exons; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism*; D007621:Karyotyping; D008297:Male; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C491731:IKBKG protein, human; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase