GeneSet Information

Tier III GS1228 • Expression patterns of the 77 genes that differentially expressed between brains of wild-type and nAChR beta-4 subunit deficient mice

DESCRIPTION:

Studies using mice with beta4 nicotinic acetylcholine receptor (nAChR) subunit deficiency (beta4-/- mice) helped reveal the roles of this subunit in bradycardiac response to vagal stimulation, nicotine-induced seizure activity and anxiety. To identify genes that might be related to beta4-containing nAChRs activity, we compared the mRNA expression profiles of brains from beta4-/- and wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes are significantly differentiated.

LABEL:

DifExprWT vs. nAChB4 KO

SCORE TYPE:

Binary

DATE ADDED:

2008-04-22

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Kedmi M, Orr-Urtreger A

TITLE:

Differential brain transcriptome of beta4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain?

JOURNAL:

Physiological genomics Jan 2007, Vol 28, pp. 213-22

ABSTRACT:

Studies using mice with beta4 nicotinic acetylcholine receptor (nAChR) subunit deficiency (beta4-/- mice) helped reveal the roles of this subunit in bradycardiac response to vagal stimulation, nicotine-induced seizure activity and anxiety. To identify genes that might be related to beta4-containing nAChRs activity, we compared the mRNA expression profiles of brains from beta4-/- and wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes significantly differentiated between these two experimental groups. Of them, the two most downregulated were spastic paraplegia 21 (human) homolog (Spg21) and 6-pyruvoyl-tetrahydropterin synthase (Pts) genes. Since the targeted mutagenesis of the beta4 nAChR subunit was done by using two mouse strains, 129SvEv and C57BL/6J, it is possible that the genes closely linked to the mutated beta4 gene represent the 129SvEv allele and not the control C57BL/6J-driven allele. We examined this possibility by using public database and quantitative RT-PCR. The expression levels of Spg21 and Pts genes that, like the beta4 gene, are localized on mouse chromosome 9, as well as the expression levels of other genes located on this chromosome, were dependent on the mouse background strain. The 67 differentially expressed genes that are not located on chromosome 9 were further analyzed for overrepresented functional annotations and transcription regulatory elements compared with the entire microarray. Genes encoding for proteins involved in tyrosine phosphatase activity, calcium ion binding, cell growth and/or maintenance, and chromosome organization were overrepresented. Our data enhance the understanding of the molecular interactions involved in the beta4 nAChR subunit function. They also emphasize the need for careful interpretation of expression microarray studies done on genetically manipulated animals. PUBMED: 16985005
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Annotation Information

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Growth (D006128)
Brain (D001921)
Paraplegia (D010264)
Gene Expression Regulation (D005786)
Chromosomes, Human, Pair 9 (D002899)
Seizures (D012640)
Alleles (D000483)
Animals (D000818)
Muscle Spasticity (D009128)
Receptors, Nicotinic (D011978)
Mice (D051379)
Chromosome Mapping (D002874)
Chromosomes (D002875)
Calcium (D002118)
Gene Expression Profiling (D020869)
Comprehension (D032882)
Maintenance (D008283)
RNA, Messenger (D012333)
Chromosomes, Mammalian (D033481)
Mice, Knockout (D018345)
Proteins (D011506)
Role (D012380)
Reverse Transcriptase Polymerase Chain Reaction (D020133)
Acetylcholine (D000109)
Tyrosine (D014443)
Oligonucleotide Array Sequence Analysis (D020411)
Mice, Inbred C57BL (D008810)
Mice, Inbred Strains (D008815)
Cells (D002477)
Transcription, Genetic (D014158)
Nerve Tissue Proteins (D009419)
Organizations (D009938)
Elements (D004602)
Mutagenesis (D016296)
Anxiety (D001007)
Mutation (D009154)
Cluster Analysis (D016000)
brain (MA:0000168)
no abnormal phenotype detected (MP:0002169)
chromosome organization (GO:0051276)
phosphatase activity (GO:0016791)
cell (GO:0005623)
ion binding (GO:0043167)
calcium ion binding (GO:0005509)
growth (GO:0040007)
binding (GO:0005488)
cell growth (GO:0016049)
chromosome (GO:0005694)

Gene List • 77 Genes

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351