RGD Reference Report - Defective calcium homeostasis in the cerebellum in a mouse model of Niemann-Pick A disease. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Defective calcium homeostasis in the cerebellum in a mouse model of Niemann-Pick A disease.

Authors: Ginzburg, L  Futerman, AH 
Citation: Ginzburg L and Futerman AH, J Neurochem. 2005 Dec;95(6):1619-28. Epub 2005 Nov 8.
RGD ID: 6482797
Pubmed: PMID:16277603   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2005.03534.x   (Journal Full-text)

We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann-Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM-/-), with reduced rates of calcium uptake via SERCA in the cerebellum of 6-7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM-/- cerebellum by 6-7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann-Pick A disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ITPR1HumanNiemann-Pick disease type A disease_progressionISOItpr1 (Mus musculus)protein:decreased expression:cerebellum (mouse)RGD 
Itpr1RatNiemann-Pick disease type A disease_progressionISOItpr1 (Mus musculus)protein:decreased expression:cerebellum (mouse)RGD 
Itpr1MouseNiemann-Pick disease type A disease_progressionIEP protein:decreased expression:cerebellum (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Itpr1  (inositol 1,4,5-trisphosphate receptor, type 1)

Genes (Mus musculus)
Itpr1  (inositol 1,4,5-trisphosphate receptor 1)

Genes (Homo sapiens)
ITPR1  (inositol 1,4,5-trisphosphate receptor type 1)


Additional Information