2010
DOI: 10.2353/ajpath.2010.090915
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Accelerated Lipofuscinosis and Ubiquitination in Granulin Knockout Mice Suggest a Role for Progranulin in Successful Aging

Abstract: Progranulin (PGRN) is involved in wound repair

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Cited by 277 publications
(334 citation statements)
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“…PGRN deficiency resulted in neuronal loss, increased gliosis, lipofuscin accumulation in the VPM/VPL, and defective myelination in the cerebral cortex. These pathological changes in aged PGRN-deficient mice are partially consistent with previous studies [11,13,33], though the brain regions examined were different. Analyses using NCL model mice in the previous studies revealed that glial activation precedes neuronal loss in the VPM/VPL [17,34].…”
Section: Discussionsupporting
confidence: 81%
“…PGRN deficiency resulted in neuronal loss, increased gliosis, lipofuscin accumulation in the VPM/VPL, and defective myelination in the cerebral cortex. These pathological changes in aged PGRN-deficient mice are partially consistent with previous studies [11,13,33], though the brain regions examined were different. Analyses using NCL model mice in the previous studies revealed that glial activation precedes neuronal loss in the VPM/VPL [17,34].…”
Section: Discussionsupporting
confidence: 81%
“…in the brain (Ahmed et al, 2010;Yin et al, 2010), we observed progressive, substantial thinning of the RNFL and a loss of ganglion cell layer (GCL) cells in 18-mo-old Grn-KO mice (Fig. 1, H-J).…”
Section: Results and Discussion Early Retinal Abnormalities In Humansmentioning
confidence: 98%
“…Histopathologically, robust microgliosis, astrogliosis, and increased ubiquitin staining are observed in the brains of aged Grn Ϫ/Ϫ mice (7,(33)(34)(35)38). Ahmed et al (7) recently showed that intracytoplasmic ubiquitinated aggregates observed in these mice are probably composed of lipofuscin.…”
Section: Mouse Models Of Progranulin Deficiencymentioning
confidence: 99%
“…Other reported behavioral deficits include depression-like behavior and either increased (35, 37) or decreased (33) anxiety. These behavioral phenotypes are fairly consistent with the clinical manifestations of FTLD, which include early behavioral problems and later deficits in memory.Histopathologically, robust microgliosis, astrogliosis, and increased ubiquitin staining are observed in the brains of aged Grn Ϫ/Ϫ mice (7,(33)(34)(35)38). Ahmed et al (7) recently showed that intracytoplasmic ubiquitinated aggregates observed in these mice are probably composed of lipofuscin.…”
mentioning
confidence: 99%