Characterization of an intestine-specific GH receptor knockout (IntGHRKO) mouse. (June 2019)

• Record Type: Journal Article
• Authors: Young, Jonathan A.; Jensen, Elizabeth A.; Stevens, Austin; Duran-Ortiz, Silvana; List, Edward O.; Berryman, Darlene E.; Kopchick, John J.
• Is Part Of: Growth hormone & IGF research. Volume 46/47(2019)
• Page Start: 5
• Page End: 15
• Publication Date: 2019-06
• Subjects: Growth hormone -- Growth hormone receptor -- Intestine; GH Growth hormone -- GHR Growth hormone receptor -- rhGH Recombinant human GH -- IBD Inflammatory bowel disease -- STAT5 Signal transducer and activator of transcription 5 -- IntGHRKO Intestinal epithelial cell-specific GHR knockout mice -- IEC Intestinal epithelial cell -- GTT Glucose tolerance test -- ITT Insulin tolerance test -- IP Intraperitoneal; Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2019.05.001
• Languages: English
• ISSNs: 1096-6374

Abstract

Abstract: Objective: Growth hormone (GH) has been reported to enhance the intestinal barrier; as such, recombinant GH has been administered for several intestinal diseases. However, excess GH action has been implicated in increasing the risk of intestinal dysfunction. The goal of this study was to examine the direct effects of GH on the small and large intestines to clarify the role GH plays in intestinal function through the use of a mouse model. Design: An intestinal epithelial-specific GH receptor (GHR) knockout (IntGHRKO) mouse line was generated using Cre-lox with the villin promoter driving Cre expression. The generated mice were characterized with respect to growth and intestinal phenotypes. Results: IntGHRKO mice showed no significant changes in body length, weight, or composition compared to floxed controls. Male IntGHRKO mice had significantly shorter large intestines at 4 and 12 months of age. Intestinal barrier function was assessed by measuring the expression of tight junction related genes, as well as levels of serum endotoxin and fecal albumin. Results showed sex differences as males had an increase in occludin levels but normal serum endotoxin and fecal albumin; while, females had changes in fecal albumin levels with normal occludin and serum endotoxin. Evaluation of glucose tolerance and fat absorption also showed sex differences as females were glucose intolerant, while males had impaired fat absorption. Histopathology revealed a trend towards decreased villus height in males, which could explain the sex difference in glucose homeostasis. Conclusions: Overall, the data demonstrate that disruption of GH on the intestinal epithelial cells modestly affects the intestinal gross anatomy, morphology, and function in a sex-specific manner. Highlights: IntGHRKO mice had normal gross morphology in most tissues. Sex-specific changes in the gut barrier were observed in IntGHRKO mice. Glucose metabolism was impaired in IntGHRKO females. IntGHRKO males had decreased fat absorption. IntGHRKO mice had similar microscopic morphology to controls.