PMID- 17990914 OWN - NLM STAT- MEDLINE DCOM- 20080812 LR - 20211020 IS - 1093-5266 (Print) IS - 1615-5742 (Electronic) IS - 1093-5266 (Linking) VI - 11 IP - 3 DP - 2008 May-Jun TI - A murine model of infantile neuronal ceroid lipofuscinosis-ultrastructural evaluation of storage in the central nervous system and viscera. PG - 185-92 AB - Infantile neuronal ceroid lipofuscinosis (INCL), also known as Santavuori-Haltia disease, is an inherited neurodegenerative disorder caused by a mutation in the gene encoding the lysosomal enzyme palmitoyl-protein-thioesterase-1 (PPT1). Fatty acid-modified proteins are not degraded and accumulate as granular osmiophilic deposits in cells in the central nervous system; patients have blindness, seizures, progressive psychomotor deterioration, and die in early childhood. Although the disease manifests clinically primarily with neurological symptoms, visceral storage also accumulates. A murine model of INCL due to PPT1 deficiency exhibits clinical findings and pathology similar to those seen in patients with INCL. Homozygous PPT1-deficient mice have a shortened life span and neurological abnormalities including seizures, blindness, and mental and motor deficits. Widespread granular osmiophilic deposits (GRODs) accumulate in lysosomes in neurons and glia in the brain, retinal cells, kidney glomerular cells, aortic smooth muscle cells, and, in lesser amounts, in the fixed-tissue macrophage system. Accumulation of GRODs in aortic smooth muscle cells is accompanied by abnormalities in cardiac function and aortic root dilatation. This PPT1-deficient murine model is a well-defined genetic system that can be used to test potential therapies for lysosomal storage disease and to study the pathophysiology of INCL. FAU - Galvin, Nancy AU - Galvin N AD - Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA. FAU - Vogler, Carole AU - Vogler C FAU - Levy, Beth AU - Levy B FAU - Kovacs, Attila AU - Kovacs A FAU - Griffey, Megan AU - Griffey M FAU - Sands, Mark S AU - Sands MS LA - eng GR - R01 DK057586/DK/NIDDK NIH HHS/United States GR - R01 NS043205/NS/NINDS NIH HHS/United States GR - R01 NS043205-05A1/NS/NINDS NIH HHS/United States GR - R56 NS043205/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20070523 PL - United States TA - Pediatr Dev Pathol JT - Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society JID - 9809673 RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (palmitoyl-protein thioesterase) SB - IM MH - Animals MH - Brain/*ultrastructure MH - Disease Models, Animal MH - Echocardiography, Doppler MH - Heart/*physiopathology MH - Inclusion Bodies/*ultrastructure MH - Mice MH - Mice, Knockout MH - Microscopy, Electron, Transmission MH - Myocardium/pathology MH - Neuronal Ceroid-Lipofuscinoses/*pathology MH - Retina/ultrastructure MH - Thiolester Hydrolases/deficiency MH - Viscera/*pathology PMC - PMC2789460 MID - NIHMS136921 EDAT- 2007/11/10 09:00 MHDA- 2008/08/13 09:00 PMCR- 2009/12/07 CRDT- 2007/11/10 09:00 PHST- 2007/02/28 00:00 [received] PHST- 2007/05/21 00:00 [accepted] PHST- 2007/11/10 09:00 [pubmed] PHST- 2008/08/13 09:00 [medline] PHST- 2007/11/10 09:00 [entrez] PHST- 2009/12/07 00:00 [pmc-release] AID - 07-03-0242 [pii] AID - 10.2350/07-03-0242.1 [doi] PST - ppublish SO - Pediatr Dev Pathol. 2008 May-Jun;11(3):185-92. doi: 10.2350/07-03-0242.1. Epub 2007 May 23.