McRae, H.M.Eccles, S.Whitehead, L.Alexander, W.S.Gécz, J.Thomas, T.Voss, A.K.2021-08-232021-08-232020Development, 2020; 147(21):1-120950-19911477-9129http://hdl.handle.net/2440/131572Börjeson-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.en© 2020. Published by The Company of Biologists Ltd.BFLSBörjeson-Forssman-Lehman SyndromeFailure to thriveGrowth hormoneGrowth hormone releasing hormoneIGF-1Insulin-like growth factor 1PHF6Plant homeodomain finger protein 6SOCS2Suppressor of cytokine signaling 2Journal article100002753910.1242/dev.1870210005905740000042-s2.0-85094683957551210Gécz, J. [0000-0002-7884-6861]