000130053 001__ 130053
000130053 005__ 20241125101150.0
000130053 0247_ $$2doi$$a10.1093/hmg/ddad199
000130053 0248_ $$2sideral$$a136344
000130053 037__ $$aART-2023-136344
000130053 041__ $$aeng
000130053 100__ $$aWilliams, Brittany N
000130053 245__ $$aHeterogeneity in the progression of retinal pathologies in mice harboring patient mimicking Impg2 mutations
000130053 260__ $$c2023
000130053 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130053 5203_ $$aBiallelic mutations in interphotoreceptor matrix proteoglycan 2 (IMPG2) in humans cause retinitis pigmentosa (RP) with early macular involvement, albeit the disease progression varies widely due to genetic heterogeneity and IMPG2 mutation type. There are currently no treatments for IMPG2-RP. To aid preclinical studies toward eventual treatments, there is a need to better understand the progression of disease pathology in appropriate animal models. Toward this goal, we developed mouse models with patient mimicking homozygous frameshift (T807Ter) or missense (Y250C) Impg2 mutations, as well as mice with a homozygous frameshift mutation (Q244Ter) designed to completely prevent IMPG2 protein expression, and characterized the trajectory of their retinal pathologies across postnatal development until late adulthood. We found that the Impg2T807Ter/T807Ter and Impg2Q244Ter/Q244Ter mice exhibited early onset gliosis, impaired photoreceptor outer segment maintenance, appearance of subretinal deposits near the optic disc, disruption of the outer retina, and neurosensorial detachment, whereas the Impg2Y250C/Y250C mice exhibited minimal retinal pathology. These results demonstrate the importance of mutation type in disease progression in IMPG2-RP and provide a toolkit and preclinical data for advancing therapeutic approaches.
000130053 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000130053 590__ $$a3.1$$b2023
000130053 591__ $$aGENETICS & HEREDITY$$b73 / 191 = 0.382$$c2023$$dQ2$$eT2
000130053 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b168 / 313 = 0.537$$c2023$$dQ3$$eT2
000130053 594__ $$a6.9$$b2023
000130053 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000130053 700__ $$aDraper, Adam
000130053 700__ $$aLang, Patrick F
000130053 700__ $$aLewis, Tylor R
000130053 700__ $$aSmith, Audrey L
000130053 700__ $$aMayerl, Steven J
000130053 700__ $$aRougié, Marie
000130053 700__ $$aSimon, Jeremy M
000130053 700__ $$aArshavsky, Vadim Y
000130053 700__ $$aGreenwald, Scott H
000130053 700__ $$aGamm, David M
000130053 700__ $$0(orcid)0000-0003-0349-9997$$aPinilla, Isabel$$uUniversidad de Zaragoza
000130053 700__ $$aPhilpot, Benjamin D
000130053 7102_ $$11013$$2646$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Oftalmología
000130053 773__ $$g33, 5 (2023), 448–464$$pHum. mol. genet.$$tHUMAN MOLECULAR GENETICS$$x0964-6906
000130053 8564_ $$s3793936$$uhttps://zaguan.unizar.es/record/130053/files/texto_completo.pdf$$yVersión publicada
000130053 8564_ $$s3077743$$uhttps://zaguan.unizar.es/record/130053/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000130053 909CO $$ooai:zaguan.unizar.es:130053$$particulos$$pdriver
000130053 951__ $$a2024-11-22-12:06:37
000130053 980__ $$aARTICLE