RGD Reference Report - Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system. - Rat Genome Database

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Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system.

Authors: Kuramoto, T  Kitada, K  Inui, T  Sasaki, Y  Ito, K  Hase, T  Kawagachi, S  Ogawa, Y  Nakao, K  Barsh, GS  Nagao, M  Ushijima, T  Serikawa, T 
Citation: Kuramoto T, etal., Proc Natl Acad Sci U S A 2001 Jan 16;98(2):559-64.
RGD ID: 67998
Pubmed: PMID:11209055   (View Abstract at PubMed)
PMCID: PMC14626   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.98.2.559   (Journal Full-text)

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.



Disease Annotations    
Tremor  (IAGP)

Gene Ontology Annotations    

Biological Process
pigmentation  (IMP)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Atrn  (attractin)

Strains
WTC.ZI-Atrnzi/Kyo  (NA)

Objects referenced in this article
Gene Atrn attractin Mus musculus
Strain SER/Kyo spontaneously epileptic rat Rattus norvegicus
Strain ZI/Kyo null Rattus norvegicus

Additional Information