title: Protein and gene expression analysis of Phf6, the gene mutated in the Börjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity.
abstract: The Plant homeodomain finger gene 6 (PHF6) was identified as the gene mutated in patients suffering from the Börjeson-Forssman-Lehmann Syndrome (BFLS), an X-linked mental retardation disorder. BFLS mental disability is evident from an early age, suggesting a developmental brain defect. The PHF6 protein contains four nuclear localisation signals and two imperfect plant homeodomain (PHD) fingers similar to the third, imperfect PHD fingers in members of the trithorax family of transcriptional regulators. The PHF6 gene is highly conserved in vertebrate species. Despite the devastating effects of mutation of the PHF6 gene, nothing is known about the cellular function of PHF6. In order to lay the base for functional studies, we identify here the cell types that express the murine Phf6 gene and protein during prenatal and postnatal development. The Phf6 gene and protein are expressed widely. However, expression levels vary from strong to barely detectable. Strongest Phf6 gene expression and nuclear localisation of Phf6 protein were observed in the developing central nervous system, the anterior pituitary gland, the primordia of facial structures and the limb buds. Expression levels of both mRNA and protein decline over the course of development. In the adult brain moderate Phf6 expression is maintained in projection neurons, such as mitral cells in the olfactory bulb, cerebrocortical pyramidal cells and cerebellar Purkinje cells. Phf6 gene expression and nuclear localisation of Phf6 protein correlate with clinical symptoms in BFLS patients, namely mental disability, pan-anterior pituitary hormonal deficiency and facial as well digit abnormalities.
authors: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Vic. 3050, Australia. avoss@wehi.edu.au
authors: Anne K
authors: AK
authors: Voss
authors: Robin
authors: R
authors: Gamble
authors: Caitlin
authors: C
authors: Collin
authors: Cheryl
authors: C
authors: Shoubridge
authors: Mark
authors: M
authors: Corbett
authors: Jozef
authors: J
authors: Gécz
authors: Tim
authors: T
authors: Thomas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins; D013577:Syndrome; D014018:Tissue Distribution
chemical_list: D018398:Homeodomain Proteins; C526788:Phf6 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins