RESUMO
The chromatin remodeler CHD5 plays a critical role in tumor suppression and neurogenesis in mammals. CHD5 contributes to gene expression during neurogenesis, but there is still much to learn regarding how this class of remodelers contributes to differentiation and development. CHD5 remodelers are vertebrate-specific, raising the prospect that CHD5 plays one or more conserved roles in this phylum. Expression of chd5 in adult fish closely mirrors expression of CHD5 in adult mammals. Knockdown of Chd5 during embryogenesis suggests new roles for CHD5 remodelers based on resulting defects in craniofacial development including reduced head and eye size as well as reduced cartilage formation in the head. In addition, knockdown of Chd5 results in altered expression of neural markers in the developing brain and eye as well as a profound defect in differentiation of dopaminergic amacrine cells. Recombinant zebrafish Chd5 protein exhibits nucleosome remodeling activity in vitro, suggesting that it is the loss of this activity that contributes to the observed phenotypes. Our studies indicate that zebrafish is an appropriate model for functional characterization of CHD5 remodelers in vertebrates and highlight the potential of this model for generating novel insights into the role of this vital class of remodelers.
Assuntos
DNA Helicases/fisiologia , Desenvolvimento Embrionário/genética , Cabeça/embriologia , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Adenosina Trifosfatases/genética , Animais , Animais Geneticamente Modificados , Encéfalo/embriologia , Encéfalo/metabolismo , Cartilagem/embriologia , Cartilagem/metabolismo , Diferenciação Celular/genética , Montagem e Desmontagem da Cromatina/genética , DNA Helicases/genética , Neurônios Dopaminérgicos/fisiologia , Embrião não Mamífero , Olho/embriologia , Olho/metabolismo , Neurogênese/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
Susac syndrome (SS) consists of a triad of vision loss, hearing loss, and encephalopathy due to autoimmune-mediated vascular endothelial injury. Herein we describe a 25-year-old previously healthy woman who presented at 20 weeks' gestation with symptoms of confusion, difficulty walking, and vision and hearing loss. She had branch-retinal artery occlusions on funduscopic examination, and sensorineural hearing loss. Additionally, non-contrast enhanced brain magnetic resonance imaging showed multiple white matter and callosal lesions consistent with ischemia. She was treated initially with aspirin, corticosteroids, and intravenous immunoglobulin with early improvement, although recurrent disease was treated with cyclophosphamide and rituximab after induction of premature delivery (at 35 weeks' gestation) to spare the fetus possible toxicity. We additionally discuss a general overview of SS, what is known about pregnancy and this disease, and issues regarding diagnostic and treatment approaches for SS during pregnancy.
