PMID- 18021406
OWN - NLM
STAT- MEDLINE
DCOM- 20080227
LR  - 20211020
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 8
DP  - 2007 Nov 16
TI  - Gene expression profiling in a mouse model of infantile neuronal ceroid 
      lipofuscinosis reveals upregulation of immediate early genes and mediators of the 
      inflammatory response.
PG  - 95
AB  - BACKGROUND: The infantile form of neuronal ceroid lipofuscinosis (also known as 
      infantile Batten disease) is caused by hereditary deficiency of a lysosomal 
      enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe 
      cortical degeneration with blindness and cognitive and motor dysfunction. The 
      PPT1-deficient knockout mouse recapitulates the key features of the disorder, 
      including seizures and death by 7-9 months of age. In the current study, we 
      compared gene expression profiles of whole brain from PPT1 knockout and normal 
      mice at 3, 5 and 8 months of age to identify temporal changes in molecular 
      pathways implicated in disease pathogenesis. RESULTS: A total of 267 genes were 
      significantly (approximately 2-fold) up- or downregulated over the course of the 
      disease. Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1) were among 
      the first genes upregulated during the presymptomatic period whereas immune 
      response genes dominated at later time points. Chemokine ligands and protease 
      inhibitors were among the most transcriptionally responsive genes. Neuronal 
      survival factors (IGF-1 and CNTF) and a negative regulator of neuronal apoptosis 
      (DAP kinase-1) were upregulated late in the course of the disease. Few genes were 
      downregulated; these included the alpha2 subunit of the GABA-A receptor, a 
      component of cortical and hippocampal neurons, and Hes5, a transcription factor 
      important in neuronal differentiation. CONCLUSION: A molecular description of 
      gene expression changes occurring in the brain throughout the course of neuronal 
      ceroid lipofuscinosis suggests distinct phases of disease progression, provides 
      clues to potential markers of disease activity, and points to new targets for 
      therapy.
FAU - Qiao, Xingwen
AU  - Qiao X
AD  - Hamon Center for Therapeutic Oncology Research and the Department of Internal 
      Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 
      xingwen.qiao@utsouthwestern.edu
FAU - Lu, Jui-Yun
AU  - Lu JY
FAU - Hofmann, Sandra L
AU  - Hofmann SL
LA  - eng
GR  - R01 NS036867/NS/NINDS NIH HHS/United States
GR  - R37 NS036867/NS/NINDS NIH HHS/United States
GR  - NS36867/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071116
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Algorithms
MH  - Animals
MH  - Disease Models, Animal
MH  - *Gene Expression Profiling
MH  - Genes, Immediate-Early/*physiology
MH  - Inflammation/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Ceroid-Lipofuscinoses/genetics/pathology/*physiopathology
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Thiolester Hydrolases/deficiency
MH  - Time Factors
MH  - Up-Regulation/*physiology
PMC - PMC2204004
EDAT- 2007/11/21 09:00
MHDA- 2008/02/28 09:00
PMCR- 2007/11/16
CRDT- 2007/11/21 09:00
PHST- 2007/04/27 00:00 [received]
PHST- 2007/11/16 00:00 [accepted]
PHST- 2007/11/21 09:00 [pubmed]
PHST- 2008/02/28 09:00 [medline]
PHST- 2007/11/21 09:00 [entrez]
PHST- 2007/11/16 00:00 [pmc-release]
AID - 1471-2202-8-95 [pii]
AID - 10.1186/1471-2202-8-95 [doi]
PST - epublish
SO  - BMC Neurosci. 2007 Nov 16;8:95. doi: 10.1186/1471-2202-8-95.