Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice

Chizuru Sogawa, Asaki Abe, Takehito Tsuji, Mitsuru Koizumi, Tsuneo Saga, Tetsuo Kunieda

Research output: Contribution to journalArticle

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Abstract

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 Ca2+. In contrast, those of normal mice (controls) expressed both cGMP and Ca2+. 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.

Original languageEnglish
Pages (from-to)822-828
Number of pages7
JournalAmerican Journal of Pathology
Volume177
Issue number2
DOIs
Publication statusPublished - Aug 2010

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C-Type Natriuretic Peptide
Gastrointestinal Tract
Genes
Dwarfism
Phenotype
Mutation
Recessive Genes
Myenteric Plexus
Gastrointestinal Motility
Nonsense Codon
Large Intestine
Pylorus
Weaning
Muscle Cells
atrial natriuretic factor receptor B
Exons
Stomach
Milk
Extremities
Alleles

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice. / Sogawa, Chizuru; Abe, Asaki; Tsuji, Takehito; Koizumi, Mitsuru; Saga, Tsuneo; Kunieda, Tetsuo.

In: American Journal of Pathology, Vol. 177, No. 2, 08.2010, p. 822-828.

Research output: Contribution to journalArticle

Sogawa, Chizuru ; Abe, Asaki ; Tsuji, Takehito ; Koizumi, Mitsuru ; Saga, Tsuneo ; Kunieda, Tetsuo. / Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice. In: American Journal of Pathology. 2010 ; Vol. 177, No. 2. pp. 822-828.
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