title: Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital cataract (HCC), is a neuronal protein.
abstract: "Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, we show that the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical pyramidal neurons, while it did not colocalize with oligodendroglial or astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from newborn mice. In the brain, Hyccin transcript levels were higher in early postnatal development (postnatal days 2 and 10) and then declined in adult mice. In a model of active myelinogenesis, organotypic cultures of rat Schwann cells (SC)/Dorsal Root Ganglion (DRG) sensory neurons, Hyccin was detected along the neurites, while it was absent from SC. Intriguingly, the abundance of the molecule was upregulated at postnatal days 10 and 15, in the initial steps of myelinogenesis and then declined at 30 days when the process is complete. As Hyccin is primarily expressed in neurons and its mutation leads to hypomyelination in human patients, we suggest that the protein is involved in neuron-to-glia signalling to initiate or maintain myelination.
authors.affiliation: Muscular and Neurodegenerative Disease Unit, G. Gaslini Institute, University of Genoa, Genoa, Italy. elisabettagazzerro@ospedale-gaslini.ge.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gazzerro
authors.forename: Simona
authors.initials: S
authors.lastname: Baldassari
authors.forename: Caterina
authors.initials: C
authors.lastname: Giacomini
authors.forename: Veronica
authors.initials: V
authors.lastname: Musante
authors.forename: Floriana
authors.initials: F
authors.lastname: Fruscione
authors.forename: Veronica
authors.initials: V
authors.lastname: La Padula
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
authors.forename: Valeria
authors.initials: V
authors.lastname: Prada
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Ian D
authors.initials: ID
authors.lastname: Duncan
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Hauke B
authors.initials: HB
authors.lastname: Werner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Lucilla
authors.initials: L
authors.lastname: Nobbio
authors.forename: Anna
authors.initials: A
authors.lastname: Corradi
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C485859:Drctnnb1a protein, mouse; D015513:Oncogene Proteins; D001616:beta-Galactosidase