Sox9 Is a Modifier of the Liver Disease Severity in a Mouse Model of Alagille Syndrome.
Alagille Syndrome
/ genetics
Animals
Bile Ducts
/ abnormalities
Cell Transdifferentiation
/ genetics
Child
Child, Preschool
Disease Models, Animal
Hepatocytes
/ cytology
Heterozygote
Humans
Infant
Jagged-1 Protein
/ genetics
Liver
/ abnormalities
Mice
Mice, Inbred C57BL
Receptors, Notch
/ genetics
SOX9 Transcription Factor
/ genetics
Severity of Illness Index
Signal Transduction
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
07
02
2019
accepted:
19
08
2019
pubmed:
31
8
2019
medline:
15
4
2021
entrez:
31
8
2019
Statut:
ppublish
Résumé
Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily by haploinsufficiency of the Notch ligand jagged1. The course of the liver disease is highly variable in ALGS. However, the genetic basis for ALGS phenotypic variability is unknown. Previous studies have reported decreased expression of the transcription factor SOX9 (sex determining region Y-box 9) in late embryonic and neonatal livers of Jag1-deficient mice. Here, we investigated the effects of altering the Sox9 gene dosage on the severity of liver disease in an ALGS mouse model. Conditional removal of one copy of Sox9 in Jag1 Our results establish Sox9 as a dosage-sensitive modifier of Jag1
Sections du résumé
BACKGROUND AND AIMS
Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily by haploinsufficiency of the Notch ligand jagged1. The course of the liver disease is highly variable in ALGS. However, the genetic basis for ALGS phenotypic variability is unknown. Previous studies have reported decreased expression of the transcription factor SOX9 (sex determining region Y-box 9) in late embryonic and neonatal livers of Jag1-deficient mice. Here, we investigated the effects of altering the Sox9 gene dosage on the severity of liver disease in an ALGS mouse model.
APPROACH AND RESULTS
Conditional removal of one copy of Sox9 in Jag1
CONCLUSIONS
Our results establish Sox9 as a dosage-sensitive modifier of Jag1
Identifiants
pubmed: 31469182
doi: 10.1002/hep.30912
pmc: PMC7048647
mid: NIHMS1047972
doi:
Substances chimiques
Jag1 protein, mouse
0
Jagged-1 Protein
0
Receptors, Notch
0
SOX9 Transcription Factor
0
Sox9 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1331-1349Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK107553
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK56338
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM130317
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK078392
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK107553
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK078640
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM084135
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK109982
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM084135
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078640
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109982
Pays : United States
Informations de copyright
© 2019 by the American Association for the Study of Liver Diseases.
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