scholarly journals Absence of WDR13 in p53-Null Mice Increases Longevity

Author(s):  
Arun Prakash Mishra ◽  
B Jyothi Lakshmi

Abstract Absence of WDR13 is known to be involved in pancreatic, colon and uterine hyperproliferation. However, a recent study showed its antiproliferative role liver regeneration in response to hepatotoxins. These findings intrigued to study the role of WDR13-null condition in Trp53 knockout mouse to study the tumour predisposition and survival. We report absence of Wdr13 in Trp53-null background alleviates the tumour load, in turn increasing total survival in mouse model.

2008 ◽  
Vol 36 (9) ◽  
pp. 1840-1845 ◽  
Author(s):  
Cuiping Chen ◽  
Jeffery L. Stock ◽  
Xingrong Liu ◽  
Jilin Shi ◽  
Jeffrey W. Van Deusen ◽  
...  

2014 ◽  
Vol 93 (5-6) ◽  
pp. 252-266 ◽  
Author(s):  
Christine B. Gurniak ◽  
Frédéric Chevessier ◽  
Melanie Jokwitz ◽  
Friederike Jönsson ◽  
Emerald Perlas ◽  
...  

2014 ◽  
Vol 13 (6) ◽  
pp. 2771-2782 ◽  
Author(s):  
Thilo Bracht ◽  
Sascha Hagemann ◽  
Marius Loscha ◽  
Dominik A. Megger ◽  
Juliet Padden ◽  
...  

2020 ◽  
Vol 134 (8) ◽  
pp. 941-953
Author(s):  
Jianxiang Xue ◽  
Linto Thomas ◽  
Maryam Tahmasbi ◽  
Alexandria Valdez ◽  
Jessica A. Dominguez Rieg ◽  
...  

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.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Honami Ogoh ◽  
Kazutsune Yamagata ◽  
Tomomi Nakao ◽  
Lisa L. Sandell ◽  
Ayaka Yamamoto ◽  
...  

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