Hyccin, the Molecule Mutated in the Leukodystrophy Hypomyelination and Congenital Cataract (HCC), Is a Neuronal Protein.

Authors

Elisabetta Gazzerro, University of Genoa, Genoa, Italy
Simona Baldassari, University of Genoa, Genoa, Italy
Caterina Giacomini, University of Genoa, Genoa, Italy
Veronica Musante, University of Genoa, Genoa, Italy
Floriana Fruscione, University of Genoa, Genoa, Italy
Veronica La Padula, University of Genoa, Genoa, Italy
Roberta Biancheri, G. Gaslini Institute, Genoa, Italy
Sonia Scarfì, University of Genoa, Genoa, Italy
Valeria Prada, University of Genoa, Genoa, Italy
Federica Sotgia, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson University, Philadelphia, PAFollow
Ian D Duncan, University of Wisconsin, Madison, WI
Federico Zara, University of Genoa, Genoa, ItalyFollow
Hauke B Werner, Max-Planck Institute of Experimental Medicine, Göttingen, Germany
Michael P Lisanti, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson University, Philadelphia, PAFollow
Lucilla Nobbio, University of Genoa, Genoa, Italy
Anna Corradi, University of Genoa, Genoa, Italy
Carlo Minetti, University of Genoa, Genoa, ItalyFollow

Document Type

Article

Publication Date

3-26-2012

Comments

This article has been peer reviewed and is published in PLoS One 2012;7(3):e32180. The published version is available at DOI: 10.1371/journal.pone.0032180. © Public Library of Science

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.

Recommended Citation

Gazzerro, Elisabetta; Baldassari, Simona; Giacomini, Caterina; Musante, Veronica; Fruscione, Floriana; La Padula, Veronica; Biancheri, Roberta; Scarfì, Sonia; Prada, Valeria; Sotgia, Federica; Duncan, Ian D; Zara, Federico; Werner, Hauke B; Lisanti, Michael P; Nobbio, Lucilla; Corradi, Anna; and Minetti, Carlo, "Hyccin, the Molecule Mutated in the Leukodystrophy Hypomyelination and Congenital Cataract (HCC), Is a Neuronal Protein." (2012). Kimmel Cancer Center Faculty Papers. Paper 19.
https://jdc.jefferson.edu/kimmelccfp/19

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

22461884