کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6022080 | 1580659 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease
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کلمات کلیدی
PBSLAMP2X-GalCD68NCLβ-galONLCTSDGFAPLAMP1neuronal ceroid lipofuscinosis - lipophuscinosis ceroid neuronalSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدSodium dodecyl sulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اتیل آمید سدیم دودسیل سولفاتphosphate buffer - بافر فسفاتβ-galactosidase - بتا گالاکتوزیدازMajor facilitator superfamily - بزرگترین تسهیل کننده خانوادگیLysosomal storage disease - بیماری ذخیره سازی لیزوزومیCluster of differentiation 68 - خوشه تمایز 68Phosphate buffered saline - فسفات بافر شورpostnuclear supernatant - فلوئور اتانولouter nuclear layer - لایه بیرونی هسته ایLysosomes - لیزوزوم هاwild type - نوع وحشیpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالLysosomal membrane protein - پروتئین غشاء لسیوزومیlysosome-associated membrane protein 1 - پروتئین غشاء مرتبط با لیزوزوم 1lysosome-associated membrane protein 2 - پروتئین غشای مرتبط با لیزوزوم 2cathepsin D - کاتهپسین DPNS - کارمندان دولت
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mutations in the major facilitator superfamily domain containing 8 (MFSD8) gene coding for the lysosomal CLN7 membrane protein result in CLN7 disease, a lysosomal storage disease of childhood. CLN7 disease belongs to a group of inherited disorders, called neuronal ceroid lipofuscinoses (NCL), which are characterized by the accumulation of autofluorescent ceroid lipopigments, neuroinflammation, photoreceptor- and neurodegeneration. We have disrupted the Mfsd8 gene by insertion of a lacZ gene-trap cassette between exons 1 and 2 in mice and have analyzed the impact of Cln7 depletion on neuronal and visceral tissues. Analysis of lacZ reporter gene activity in heterozygous Mfsd8(wt/tm1a) mice showed strong Mfsd8 mRNA expression in the cerebral cortex, in the hippocampus and in the kidney. Homozygous Mfsd8(tm1a/tm1a) mice were viable and fertile and resembled biochemically the NCL-phenotype of human CLN7 patients including the accumulation of autofluorescent material in the brain and peripheral tissues and of subunit c of mitochondrial ATP synthase in the cerebellum and nuclei of distinct brain regions, and the degeneration of photoreceptor cells in the retina. Lysosomal storage was found in large neurons of the medulla, the hippocampus and in Purkinje cells of the cerebellum in mutant mice. The ultrastructure of the storage material revealed dense lamellar bodies with irregular forms within cerebellar and hippocampal neurons. In the brain loss of Cln7 was accompanied by mild reactive microgliosis and subtle astrogliosis by 10Â months of age, respectively. In summary we have generated a mouse model which is partly valuable as some but not all neuropathological features of human CLN7 disease are recapitulated thus representing an animal model to study CLN7-specific disease mechanisms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 65, May 2014, Pages 12-24
Journal: Neurobiology of Disease - Volume 65, May 2014, Pages 12-24
نویسندگان
Markus Damme, Laura Brandenstein, Susanne Fehr, Wanda Jankowiak, Udo Bartsch, Michaela Schweizer, Irm Hermans-Borgmeyer, Stephan Storch,