PMID- 16368706
OWN - NLM
STAT- MEDLINE
DCOM- 20060413
LR  - 20071114
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 15
IP  - 3
DP  - 2006 Feb 1
TI  - Targeted disruption of glycerol kinase gene in mice: expression analysis in liver 
      shows alterations in network partners related to glycerol kinase activity.
PG  - 405-15
AB  - Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with 
      metabolic and neurological crises. Liver shows the highest level of glycerol 
      kinase (GK) activity in humans and mice. Absence of genotype-phenotype 
      correlations in patients with GKD indicates the involvement of modifier genes, 
      including other network partners. To understand the molecular pathogenesis of 
      GKD, we performed microarray analysis on liver mRNA from neonatal glycerol kinase 
      (Gyk) knockout (KO) and wild-type (WT) mice. Unsupervised learning revealed that 
      the overall gene expression profile of the KO mice was different from that of WT. 
      Real-time PCR confirmed the differences for selected genes. Functional gene 
      enrichment analysis was used to find 56 increased and 37 decreased gene 
      functional categories. PathwayAssist analysis identified changes in gene 
      expression levels of genes involved in organic acid metabolism indicating that GK 
      was part of the same metabolic network which correlates well with the patients 
      with GKD having metabolic acidemia during their episodic crises. Network 
      component analysis (NCA) showed that transcription factors sterol regulatory 
      element-binding protein (SREBP)-1c, carbohydrate response element-binding protein 
      (ChREBP), hepatocyte nuclear factor-4 alpha (HNF-4alpha) and peroxisome 
      proliferative-activated receptor-alpha (PPARalpha) had increased activity in the 
      Gyk KO mice compared with WT mice, whereas SREBP-2 was less active in the Gyk KO 
      mice. These studies show that Gyk deletion causes alterations in expression of 
      genes in several regulatory networks and is the first time NCA has been used to 
      expand on microarray data from a mouse KO model of a human disease.
FAU - MacLennan, Nicole K
AU  - MacLennan NK
AD  - Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, 
      CA 90095-7088, USA.
FAU - Rahib, Lola
AU  - Rahib L
FAU - Shin, Cynthia
AU  - Shin C
FAU - Fang, Zixing
AU  - Fang Z
FAU - Horvath, Steve
AU  - Horvath S
FAU - Dean, Jason
AU  - Dean J
FAU - Liao, James C
AU  - Liao JC
FAU - McCabe, Edward R B
AU  - McCabe ER
FAU - Dipple, Katrina M
AU  - Dipple KM
LA  - eng
GR  - K08 DK60055/DK/NIDDK NIH HHS/United States
GR  - R01 GM67929/GM/NIGMS NIH HHS/United States
GR  - R01 HD22563/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051220
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA Probes)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.30 (Glycerol Kinase)
SB  - IM
MH  - Animals
MH  - Cluster Analysis
MH  - DNA Probes
MH  - *Gene Expression Regulation, Enzymologic
MH  - Gene Targeting
MH  - Glycerol Kinase/*genetics/*metabolism
MH  - Liver/*enzymology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microarray Analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/metabolism
EDAT- 2005/12/22 09:00
MHDA- 2006/04/14 09:00
CRDT- 2005/12/22 09:00
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2006/04/14 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
AID - ddi457 [pii]
AID - 10.1093/hmg/ddi457 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2006 Feb 1;15(3):405-15. doi: 10.1093/hmg/ddi457. Epub 2005 Dec 
      20.