Document Detail


Identification of novel mouse genes conferring posthypoxic pauses.
MedLine Citation:
PMID:  22539170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1(A/J)/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis.
Authors:
C Barton Gillombardo; Motoo Yamauchi; Mark D Adams; Jesse Dostal; Sam Chai; Michael W Moore; Lucas M Donovan; Fang Han; Kingman P Strohl
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-26
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-12-07     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-74     Citation Subset:  IM    
Affiliation:
Division of Pulmonary, Critical Care, and Sleep Medicine, University Hospital Case Medical Center and the Louis Stokes Cleveland DVA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoprotein A-II / genetics*
Chromosome Mapping
Female
Male
Medulla Oblongata / metabolism
Mice
Mice, Inbred C57BL
Periodicity
Pons / metabolism
Quantitative Trait Loci*
Respiration / genetics*
Grant Support
ID/Acronym/Agency:
NS-052452/NS/NINDS NIH HHS; UL1 RR-024989/RR/NCRR NIH HHS; UL1 RR024989/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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