Alimentary TractEnhanced survival and mucosal repair after dextran sodium sulfate–induced colitis in transgenic mice that overexpress growth hormone☆,☆☆
Section snippets
Transgenic mice
MT1-bGH-TG breeder pairs on a C57BL6/SJL genetic background were provided by Drs. Richard Palmiter, Ralph Brinster, and Richard Behringer.32 Hemizygous MT1-bGH-TG males were mated with WT C57BL6/SJL females (Jackson Laboratories, Bar Harbor, ME) to provide MT1-bGH-TG and WT littermates for the experiments. MT1-bGH-TG mice are readily distinguished from WT by increased body weight, which is evident by postnatal day 28. Genotype was verified on selected mice by polymerase chain reaction (PCR) on
GH excess enhances survival during DSS-induced colitis and recovery
All MT1-bGH-TG and WT mice survived 5 days of treatment with 4% DSS, but there was 25% mortality of MT1-bGH-TG mice and 50% mortality of WT mice during the 10 days after cessation of 4% DSS. Therefore, this dose of DSS was not used further. With a 3% dose of DSS, 100% of MT1-bGH-TG and WT mice survived the 5-day treatment with DSS. During recovery, 100% of MT1-bGH-TG (30 animals) survived the entire recovery phase, whereas 6 of 30 WT did not survive until the designated study time. MT1-bGH-TG
Discussion
This study shows that chronic elevation of plasma GH did not have a significant protective effect on the onset or severity of acute colitis induced by DSS or associated mucosal damage. GH excess did, however, improve survival during recovery from colitis, promote remission of inflammation, and enhance mucosal repair. The more precipitous weight loss in the WT mice that did not survive the recovery period compared with MT1-bGH-TG supports the concept that anabolic effects of GH to maintain body
Acknowledgements
The authors thank Dr. John Woosley for assistance with pathology, Eileen Hoyt for assistance with image analyses, Evonne Bruton for assistance with radioimmunoassays, Kirk McNaughton for assistance with histology, and Deborah Carver for secretarial assistance.
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Cited by (0)
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Supported by a predoctoral fellowship from the Howard Hughes Medical Foundation (to K.L.W.), a grant from the Crohn's and Colitis Foundation of America, and National Institutes of Health grant DK47709 (to P.K.L. and R.B.S.). The study was facilitated by the molecular histopathology core of the Center for Gastrointestinal Biology and Disease (NIH P30-DK-34987) and mouse pathology, tissue culture, and DNA synthesis cores of the Lineberger Cancer Center (NIH CA16086).
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Address requests for reprints to: Kristen L. Williams, B.S., Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545. e-mail: [email protected]; fax: (919) 966-6927.