RRC ID |
31342
|
著者 |
Hafler BP, Klein ZA, Jimmy Zhou Z, Strittmatter SM.
|
タイトル |
Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice.
|
ジャーナル |
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.
|
巻・号 |
1588
|
ページ |
168-74
|
公開日 |
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
|
引用数 |
14
|
WOS 分野
|
NEUROSCIENCES
|
リソース情報 |
実験動物マウス |
RBRC02370 |