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Series GSE39621 Query DataSets for GSE39621
Status Public on Dec 27, 2012
Title Expression data from brain, liver and spleen of Npc1-/- mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional neurological, lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1-/- mice (Npc1nih)relative to Npc1+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates for the neurological disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gaucher’s disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1-/- as well as Balb/c Npc1nmf164 mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry.
We used microarrays on the diseased organs, brain, liver and spleen of the Npc1-/- mice to unserstand the molecular changes occur during the progression of NPC diseases. From the data, we have identified 12 potential genes which can be potentially developed as blood-based biomarker. We have also discovered up regulation of innate iimunity genes in all three organs of Npc1-/- mice and functionally validated them in liver and spleen.
Overall design Brain from 11 female Npc1−/− and 16 control female mice (Npc1+/+ and Npc1+/−) from 6 age groups (20-25, 37-40, 54-55, 59-62, 67-71 and 81-84 days) were surgically harvested. Liver and spleen from 6 Npc1-/- and 6 Npc1+/- female mice from three age group ( 20-25, 54-55 and 67-71 days) were surgically harvested. Organs were kept in RNA later and stored at -20 °C until used. RNA was isolated and Affymetrix mouse 430 2.0 array hybridizations were performed by ‘UCLA Clinical Microarray Core’, UCLA, Los Angeles, CA, USA. Subsequent raw data were analyzed using DNA-Chip Analyzer (D-Chip) with the .CEL files obtained from AGCC. Data from Npc1-/- mice from all age groups were compared to control mice (Npc1+/- and/or Npc1-/- mice) from all age groups separately for brain, liver and spleen. 'Matrix Table1' corrsponds for brain, 'Matrix Table2' corresponds for liver and 'Matrix Table3' corresponds for spleen. Thresholds for selecting significant genes were set at a relative difference ³1.5-fold, absolute difference ³100 signal intensity units and p<0.05. Genes that met all three criteria simultaneously were considered as significant change.
Contributor(s) Alam S, Shin J, Tamez P, Haldar K
Citation(s) 23094108
Submission date Jul 24, 2012
Last update date Feb 11, 2019
Contact name Md Suhail Alam
Phone 574-631-3227
Organization name University of Notre Dame
Department Center for Rare and Neglected Diseases/Biological Sciences
Lab Haldar lab
Street address 103 Galvin, University of Notre Dame, IN
City Notre Dame
State/province IN Indiana
ZIP/Postal code 46545
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (51)
GSM973238 WT Brain 20d Mouse1
GSM973239 WT Brain 25d Mouse1
GSM973240 HET Brain 20d Mouse1
BioProject PRJNA171263

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39621_Matrix_Table_1_Brain.txt.gz 5.9 Mb (ftp)(http) TXT
GSE39621_Matrix_Table_2_Liver.txt.gz 3.9 Mb (ftp)(http) TXT
GSE39621_Matrix_Table_3_Spleen.txt.gz 3.9 Mb (ftp)(http) TXT
GSE39621_RAW.tar 182.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table
Processed data is available on Series record

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