Downregulation of the GHRH/GH/IGF1 axis in a mouse model of Börjeson-Forssman-Lehman syndrome.
Helen M McRaeSamantha EcclesLachlan WhiteheadWarren S AlexanderJozef GeczTim ThomasAnne Kathrin VossPublished in: Development (Cambridge, England) (2020)
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.
Keyphrases
- growth hormone
- mouse model
- intellectual disability
- autism spectrum disorder
- transcription factor
- poor prognosis
- signaling pathway
- cell proliferation
- genome wide
- gene expression
- adipose tissue
- resting state
- high fat diet induced
- subarachnoid hemorrhage
- long non coding rna
- smoking cessation
- bioinformatics analysis
- cell wall