RRC ID 31342
Author Hafler BP, Klein ZA, Jimmy Zhou Z, Strittmatter SM.
Title Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice.
Journal Brain Res
Abstract Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn(-/-) mice develop degenerative pathology similar to features of human CLN11.
Volume 1588
Pages 168-74
Published 2014-11-7
DOI 10.1016/j.brainres.2014.09.023
PII S0006-8993(14)01234-7
PMID 25234724
PMC PMC4254024
MeSH Animals Cells, Cultured Electroretinography Granulins Immunohistochemistry Intercellular Signaling Peptides and Proteins / deficiency* Intercellular Signaling Peptides and Proteins / genetics Mice, Inbred C57BL Mice, Knockout Microscopy, Confocal Neuronal Ceroid-Lipofuscinoses Optical Imaging Photoreceptor Cells, Vertebrate / pathology Photoreceptor Cells, Vertebrate / physiology Progranulins Retinal Degeneration / pathology Retinal Degeneration / physiopathology* Retinal Ganglion Cells / pathology Retinal Ganglion Cells / physiology
IF 2.733
Times Cited 14
Mice RBRC02370