Characterization of samhd1 Morphant Zebrafish Recapitulates Features of the Human Type I Interferonopathy Aicardi-Goutières Syndrome

摘要: In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form Aicardi-Goutieres syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation IFN-stimulated genes (ISGs). particular, SAMHD1-related AGS is associated with distinctive cerebrovascular pathology that commonly leads to stroke. Although inflammatory responses are observed immune cells cultured from Samhd1 null mouse models, these mice physically healthy, specifically lacking brain phenotype. We have investigated use zebrafish as alternative system for generating clinically relevant model AGS. Using temporal knockdown samhd1, we observe hindbrain ventricular swelling hemorrhage. Furthermore, samhd1 or another AGS-associated gene, adar, significant innate immune-related increase number expressing ifnphi1. To our knowledge, this first example vivo recapitulates features both neurological characteristics disease. The phenotypes adar suggest controlling processes conserved zebrafish, thereby also contributing understanding antiviral signaling organism.