Document Detail

Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice.
MedLine Citation:
PMID:  20616347     Owner:  NLM     Status:  MEDLINE    
Natriuretic peptide receptor B (NPR-B), which has high affinity for C-type natriuretic peptide (CNP) and synthesizes intracellular cGMP, may be involved in gastrointestinal tract (GIT) regulation. A mutant allele of the NPR-B-encoding gene (Npr2) is responsible for the phenotype of the short-limb dwarfism (SLW) mouse. Homozygosity for this autosomal-recessive gene (slw/slw) leads to dwarfism and death before weaning because of milk retention in the stomach and intestinal distention. To elucidate the relationship between CNP/NPR-B signaling and GIT function, we investigated the association between Npr2 mutation and the GIT phenotype in slw/slw mice. The pylorus and large intestine of the mutants did not respond to CNP stimulation; further, they showed pyloric lumen narrowing with randomly aligned circular muscle cells. Comparison of the cGMP and neuronal marker distribution in GIT tissues confirmed cGMP expression in neuronal tissues. An Auerbach's plexus and submucosal tissues of the mutants didn't express cGMP and expressed Ca(2+). In contrast, those of normal mice (controls) expressed both cGMP and Ca(2+). Sequencing revealed that the causative Npr2 mutation was a 7-base deletion in exon 8, resulting in a frameshift and premature termination codon appearance. Therefore, the GIT phenotype of slw/slw mice is because of a CNP/NPR-B-signaling defect caused by an Npr2 mutation. These results facilitate better understanding of the role of CNP/NPR-B signaling in GIT motility.
Chizuru Sogawa; Asaki Abe; Takehito Tsuji; Mitsuru Koizumi; Tsuneo Saga; Tetsuo Kunieda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-08
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-03     Completed Date:  2011-01-25     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  822-8     Citation Subset:  AIM; IM    
Department of Animal Genetics, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
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MeSH Terms
Calcium / metabolism
Cyclic GMP / metabolism
DNA Mutational Analysis
Gastrointestinal Diseases / genetics*
Gastrointestinal Tract / anatomy & histology,  physiology,  physiopathology
Mice, Inbred C57BL
Mice, Inbred Strains
Muscle, Smooth / physiology
Natriuretic Peptide, C-Type / metabolism
Receptors, Atrial Natriuretic Factor / genetics*,  metabolism
Reg. No./Substance:
127869-51-6/Natriuretic Peptide, C-Type; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP; EC, Atrial Natriuretic Factor; EC natriuretic factor receptor B

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