PUBLICATION

A zebrafish model of growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1)

Authors
Heidary, S., Awasthi, N., Page, N., Allnutt, T., Lewis, R.S., Liongue, C., Ward, A.C.
ID
ZDB-PUB-230331-45
Date
2023
Source
Cellular and molecular life sciences : CMLS   80: 109109 (Journal)
Registered Authors
Liongue, Clifford, Ward, Alister C.
Keywords
GHISID, Growth, Growth hormone, Immunity, STAT5, Zebrafish
MeSH Terms
  • Animals
  • Growth Hormone/genetics
  • Humans
  • Laron Syndrome*/genetics
  • Mutation
  • STAT5 Transcription Factor/genetics
  • Zebrafish*/genetics
PubMed
36995466 Full text @ Cell. Mol. Life Sci.
Abstract
Signal transducer and activator of transcription (STAT) proteins act downstream of cytokine receptors to facilitate changes in gene expression that impact a range of developmental and homeostatic processes. Patients harbouring loss-of-function (LOF) STAT5B mutations exhibit postnatal growth failure due to lack of responsiveness to growth hormone as well as immune perturbation, a disorder called growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1). This study aimed to generate a zebrafish model of this disease by targeting the stat5.1 gene using CRISPR/Cas9 and characterising the effects on growth and immunity. The zebrafish Stat5.1 mutants were smaller, but exhibited increased adiposity, with concomitant dysregulation of growth and lipid metabolism genes. The mutants also displayed impaired lymphopoiesis with reduced T cells throughout the lifespan, along with broader disruption of the lymphoid compartment in adulthood, including evidence of T cell activation. Collectively, these findings confirm that zebrafish Stat5.1 mutants mimic the clinical impacts of human STAT5B LOF mutations, establishing them as a model of GHISID1.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping