Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Sci (Lond) ; 134(8): 941-953, 2020 04 30.
Article in English | MEDLINE | ID: mdl-32227118

ABSTRACT

The sodium-hydrogen exchanger isoform 3 (NHE3, SLC9A3) is abundantly expressed in the gastrointestinal tract and is proposed to play essential roles in Na+ and fluid absorption as well as acid-base homeostasis. Mutations in the SLC9A3 gene can cause congenital sodium diarrhea (CSD). However, understanding the precise role of intestinal NHE3 has been severely hampered due to the lack of a suitable animal model. To navigate this problem and better understand the role of intestinal NHE3, we generated a tamoxifen-inducible intestinal epithelial cell-specific NHE3 knockout mouse model (NHE3IEC-KO). Before tamoxifen administration, the phenotype and blood parameters of NHE3IEC-KO were unremarkable compared with control mice. After tamoxifen administration, NHE3IEC-KO mice have undetectable levels of NHE3 in the intestine. NHE3IEC-KO mice develop watery, alkaline diarrhea in combination with a swollen small intestine, cecum and colon. The persistent diarrhea results in higher fluid intake. After 3 weeks, NHE3IEC-KO mice show a ∼25% mortality rate. The contribution of intestinal NHE3 to acid-base and Na+ homeostasis under normal conditions becomes evident in NHE3IEC-KO mice that have metabolic acidosis, lower blood bicarbonate levels, hyponatremia and hyperkalemia associated with drastically elevated plasma aldosterone levels. These results demonstrate that intestinal NHE3 has a significant contribution to acid-base, Na+ and volume homeostasis, and lack of intestinal NHE3 has consequences on intestinal structural integrity. This mouse model mimics and explains the phenotype of individuals with CSD carrying SLC9A3 mutations.


Subject(s)
Abnormalities, Multiple/genetics , Diarrhea/congenital , Epithelial Cells/metabolism , Metabolism, Inborn Errors/genetics , Sodium-Hydrogen Exchanger 3/genetics , Abnormalities, Multiple/metabolism , Abnormalities, Multiple/mortality , Abnormalities, Multiple/pathology , Animals , Diarrhea/genetics , Diarrhea/metabolism , Diarrhea/mortality , Diarrhea/pathology , Disease Models, Animal , Female , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Metabolism, Inborn Errors/metabolism , Metabolism, Inborn Errors/mortality , Metabolism, Inborn Errors/pathology , Mice , Mice, Knockout , Mutation , Sodium-Hydrogen Exchanger 3/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...