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 language | English |
|---|---|
| Pages (from-to) | 822-828 |
| Number of pages | 7 |
| Journal | American Journal of Pathology |
| Volume | 177 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice
AU - Sogawa, Chizuru
AU - Abe, Asaki
AU - Tsuji, Takehito
AU - Koizumi, Mitsuru
AU - Saga, Tsuneo
AU - Kunieda, Tetsuo
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77957254584&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2010.091278
DO - 10.2353/ajpath.2010.091278
M3 - Article
VL - 177
SP - 822
EP - 828
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -