| First Author | McRae HM | Year | 2020 |
| Journal | Development | Volume | 147 |
| Issue | 21 | PubMed ID | 32994169 |
| Mgi Jnum | J:299742 | Mgi Id | MGI:6490765 |
| Doi | 10.1242/dev.187021 | Citation | McRae HM, et al. (2020) Downregulation of the GHRH/GH/IGF1 axis in a mouse model of Borjeson-Forssman-Lehman syndrome. Development 147(21):dev187021 |
| abstractText | Borjeson-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. |
