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Transl Psychiatry ; 3: e254, 2013 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-23632458

RESUMEN

Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.


Asunto(s)
Glicoproteínas de Membrana/genética , Proteínas del Tejido Nervioso/genética , Trastornos Fóbicos/genética , Adulto , Amígdala del Cerebelo/química , Animales , Conducta Animal , Electrorretinografía , Femenino , Ingeniería Genética/métodos , Heterocigoto , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Pruebas Psicológicas , Reflejo de Sobresalto/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estrés Psicológico/genética
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