Downregulation of the GHRH/GH/IGF1 axis in a mouse model of Börjeson-Forssman-Lehman syndrome

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dc.contributor.authorMcRae, H.M.
dc.contributor.authorEccles, S.
dc.contributor.authorWhitehead, L.
dc.contributor.authorAlexander, W.S.
dc.contributor.authorGécz, J.
dc.contributor.authorThomas, T.
dc.contributor.authorVoss, A.K.
dc.date.issued2020
dc.description.abstractBörjeson-Forssman-Lehmann syndrome (BFLS) is an intellectual disability and endocrine disorder caused by plant homeodomain finger 6 (PHF6) mutations. Individuals with BFLS present with short stature. We report a mouse model of BFLS, in which deletion of Phf6 causes a proportional reduction in body size compared with control mice. Growth hormone (GH) levels were reduced in the absence of PHF6. Phf6 - /Y animals displayed a reduction in the expression of the genes encoding GH-releasing hormone (GHRH) in the brain, GH in the pituitary gland and insulin-like growth factor 1 (IGF1) in the liver. Phf6 deletion specifically in the nervous system caused a proportional growth defect, indicating a neuroendocrine contribution to the phenotype. Loss of suppressor of cytokine signaling 2 (SOCS2), a negative regulator of growth hormone signaling partially rescued body size, supporting a reversible deficiency in GH signaling. These results demonstrate that PHF6 regulates the GHRH/GH/IGF1 axis.
dc.description.statementofresponsibilityHelen M. McRae, Samantha Eccles, Lachlan Whitehead, Warren S. Alexander, Jozef Gécz, Tim Thomas and Anne K. Voss
dc.identifier.citationDevelopment, 2020; 147(21):1-12
dc.identifier.doi10.1242/dev.187021
dc.identifier.issn0950-1991
dc.identifier.issn1477-9129
dc.identifier.orcidGécz, J. [0000-0002-7884-6861]
dc.identifier.urihttp://hdl.handle.net/2440/131572
dc.language.isoen
dc.publisherThe Company of Biologists
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1029481
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1161111
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1113577
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1091593
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1176789
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058344
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1155224
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1081421
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1003435
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/575512
dc.rights© 2020. Published by The Company of Biologists Ltd.
dc.source.urihttps://doi.org/10.1242/dev.187021
dc.subjectBFLS
dc.subjectBörjeson-Forssman-Lehman Syndrome
dc.subjectFailure to thrive
dc.subjectGrowth hormone
dc.subjectGrowth hormone releasing hormone
dc.subjectIGF-1
dc.subjectInsulin-like growth factor 1
dc.subjectPHF6
dc.subjectPlant homeodomain finger protein 6
dc.subjectSOCS2
dc.subjectSuppressor of cytokine signaling 2
dc.titleDownregulation of the GHRH/GH/IGF1 axis in a mouse model of Börjeson-Forssman-Lehman syndrome
dc.typeJournal article
pubs.publication-statusPublished

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