Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system
| Autor: | Yoshihiro Ogawa, Takashi Kuramoto, Kazuhiro Kitada, Toshihide Inui, Kazuwa Nakao, Toshikazu Ushijima, Gregory S. Barsh, Saburo Kawagachi, Yoshifumi Sasaki, Tadao Serikawa, Minako Nagao, Takao Hase, Kazumi Ito |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Chromosomes Human Pair 20 Energy homeostasis Animals Genetically Modified Myelin Mice Central Nervous System Diseases Tremor Myelin Sheath Expressed Sequence Tags Multidisciplinary Chromosome Mapping Exons Biological Sciences Cell biology medicine.anatomical_structure Phenotype Agouti Signaling Protein Intercellular Signaling Peptides and Proteins Muscle Hypotonia Female Neuroglia Gene isoform DNA Complementary Positional cloning Transgene Central nervous system Molecular Sequence Data Nerve Tissue Proteins Biology Rats Mutant Strains Mice Neurologic Mutants Species Specificity medicine Animals Humans Hair Color Gene Glycoproteins Brain Chemistry Paraplegia Alternative splicing Genetic Complementation Test Membrane Proteins Proteins Molecular biology Axons Introns Rats Genes Vacuoles Energy Metabolism |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 98(2) |
| ISSN: | 0027-8424 |
| Popis: | The rat zitter ( zi ) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin ( Atrn ) mRNA in the brain of the zi / zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte–T cell interaction, agouti -related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany ( mg ) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi / zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases. |
| Databáze: | OpenAIRE |
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