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

Date

2020

Authors

McRae, H.M.
Eccles, S.
Whitehead, L.
Alexander, W.S.
Gécz, J.
Thomas, T.
Voss, A.K.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Development, 2020; 147(21):1-12

Statement of Responsibility

Helen M. McRae, Samantha Eccles, Lachlan Whitehead, Warren S. Alexander, Jozef Gécz, Tim Thomas and Anne K. Voss

Conference Name

DOI

10.1242/dev.187021

Abstract

Börjeson-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.

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Dissertation Note

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Description

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Rights

© 2020. Published by The Company of Biologists Ltd.

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Grant ID

http://purl.org/au-research/grants/nhmrc/1029481
 http://purl.org/au-research/grants/nhmrc/1161111
 http://purl.org/au-research/grants/nhmrc/1113577
 http://purl.org/au-research/grants/nhmrc/1091593
 http://purl.org/au-research/grants/nhmrc/1176789
 http://purl.org/au-research/grants/nhmrc/1058344
 http://purl.org/au-research/grants/nhmrc/1155224
 http://purl.org/au-research/grants/nhmrc/1081421
 http://purl.org/au-research/grants/nhmrc/1003435
 http://purl.org/au-research/grants/nhmrc/575512

Published Version

https://doi.org/10.1242/dev.187021

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Persistent link to this record

http://hdl.handle.net/2440/131572