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Series GSE3843 Query DataSets for GSE3843
Status Public on Dec 22, 2005
Title Targeted disruption of glycerol kinase gene in mice: expression analysis in liver
Organism Mus musculus
Experiment type Expression profiling by array
Summary Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with metabolic and neurologic crises. Liver shows the highest level of glycerol kinase (GK) activity in humans and mice. Absence of genotype-phenotype correlations in patients with GKD indicate 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 the overall gene expression profile of the KO mice was different from that of WT. Real time PCR confirmed differences for selected genes. Functional gene enrichment analysis was used to find 56 increased and 37 decreased gene functional categories. Pathway Assist 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 SREBP-1c, ChREBP, HNF-4alpha, and PPAR-alpha, had increased activity in the Gyk KO mice compared with WT mice; while SREBP-2 was less active in the Gyk KO mice. These studies show that Gyk deletion causes alterations in gene expression of genes in several regulatory networks and is the first time NCA has been used to expand on microarray data from a mouse knockout model of a human disease.
Keywords: Glycerol kinase (Gyk) knockout mouse; mouse model of human Glycerol Kinase Deficiency; Gyk KO versus WT liver expression analysis; Affymetrix mus 430 2.0 GeneChip
Overall design Male WT and KO mouse pups were sacrificed on day of life (dol) 3 and each liver was harvested. Total RNA from 4 KO and 4 WT livers was isolated individually. cDNA was synthesized from the poly(A)+ mRNA in the total RNA, Biotin-tagged and fragmented to an average strand length of 100 bases (range 35-200 bases). Ten µg of each cRNA was hybridized onto an Affymetrix mus 430 2.0 GeneChip to analyze differences in liver gene expression between KO and WT mice. Day of life three was chosen because the mice are phenotypically symptomatic with statistically different parameters for hypoglycemia, acidosis; low bicarbonate and decreased base excess. On day of life 2 they are not significantly different from wild type in all of these important clinical phenotypes.
Contributor(s) MacLennan NK, Rahib L, Shin C, Fang Z, Horvath S, Dean J, Liao JC, McCabe E, Dipple KM
Citation(s) 16368706
Submission date Dec 15, 2005
Last update date Feb 11, 2019
Contact name Nicole Kim MacLennan
Phone 310-206-3050
Organization name University of California, Los Angeles
Department Pediatrics
Lab McCabe
Street address 10833 LeConte Ave
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (8)
GSM87833 Liver_WildType_1
GSM87834 Liver_WildType_2
GSM87835 Liver_WildType_3
BioProject PRJNA94063

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