Your browser doesn't support javascript.
loading
A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis.
Vukadin, Lana; Park, Bohye; Mohamed, Mostafa; Li, Huashi; Elkholy, Amr; Torrelli-Diljohn, Alex; Kim, Jung-Hyun; Jeong, Kyuho; Murphy, James M; Harvey, Caitlin A; Dunlap, Sophia; Gehrs, Leah; Lee, Hanna; Kim, Hyung-Gyoon; Sah, Jay Prakash; Lee, Seth N; Stanford, Denise; Barrington, Robert A; Foote, Jeremy B; Sorace, Anna G; Welner, Robert S; Hildreth, Blake E; Lim, Ssang-Taek Steve; Ahn, Eun-Young Erin.
Afiliação
  • Vukadin L; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Park B; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Mohamed M; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Li H; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Elkholy A; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Torrelli-Diljohn A; Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Kim JH; Metastasis Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi-do, South Korea.
  • Jeong K; Department of Medicine, College of Medicine, Dongguk University, Gyeongju, South Korea.
  • Murphy JM; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Harvey CA; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Dunlap S; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Gehrs L; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Lee H; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Kim HG; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Sah JP; Department of Pathology, Division of Molecular and Cellular Pathology, and.
  • Lee SN; Department of Radiology and.
  • Stanford D; Department of Medicine, Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Barrington RA; Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.
  • Foote JB; Department of Microbiology.
  • Sorace AG; Department of Radiology and.
  • Welner RS; O'Neal Comprehensive Cancer Center, and.
  • Hildreth BE; O'Neal Comprehensive Cancer Center, and.
  • Lim SS; Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Ahn EE; Department of Pathology, Division of Molecular and Cellular Pathology, and.
JCI Insight ; 9(5)2024 Mar 08.
Article em En | MEDLINE | ID: mdl-38290089
ABSTRACT
Rare diseases are underrepresented in biomedical research, leading to insufficient awareness. Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare disease caused by genetic alterations that result in heterozygous loss of function of SON. While patients with ZTTK syndrome live with numerous symptoms, the lack of model organisms hampers our understanding of SON and this complex syndrome. Here, we developed Son haploinsufficiency (Son+/-) mice as a model of ZTTK syndrome and identified the indispensable roles of Son in organ development and hematopoiesis. Son+/- mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis. Furthermore, we identified hematopoietic abnormalities in Son+/- mice, including leukopenia and immunoglobulin deficiency, similar to those observed in human patients. Surface marker analyses and single-cell transcriptome profiling of hematopoietic stem and progenitor cells revealed that Son haploinsufficiency shifted cell fate more toward the myeloid lineage but compromised lymphoid lineage development by reducing genes required for lymphoid and B cell lineage specification. Additionally, Son haploinsufficiency caused inappropriate activation of erythroid genes and impaired erythropoiesis. These findings highlight the importance of the full gene expression of Son in multiple organs. Our model serves as an invaluable research tool for this rare disease and related disorders associated with SON dysfunction.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Raras / Hematopoese Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Raras / Hematopoese Idioma: En Ano de publicação: 2024 Tipo de documento: Article