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Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

Publication ,  Journal Article
Nagy, E; Rodriguiz, RM; Wetsel, WC; MacIver, NJ; Hale, LP
Published in: PLoS One
2016

Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC), using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice). Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams) that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type (WT) pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and for development of therapies to prevent reproductive complications and/or growth failure in humans with IBD.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0152764

Location

United States

Related Subject Headings

  • Reproduction
  • Mice
  • Inflammatory Bowel Diseases
  • General Science & Technology
  • Disease Models, Animal
  • Animals
 

Citation

APA
Chicago
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Nagy, E., Rodriguiz, R. M., Wetsel, W. C., MacIver, N. J., & Hale, L. P. (2016). Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease. PLoS One, 11(4), e0152764. https://doi.org/10.1371/journal.pone.0152764
Nagy, Eniko, Ramona M. Rodriguiz, William C. Wetsel, Nancie J. MacIver, and Laura P. Hale. “Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.PLoS One 11, no. 4 (2016): e0152764. https://doi.org/10.1371/journal.pone.0152764.
Nagy E, Rodriguiz RM, Wetsel WC, MacIver NJ, Hale LP. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease. PLoS One. 2016;11(4):e0152764.
Nagy, Eniko, et al. “Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.PLoS One, vol. 11, no. 4, 2016, p. e0152764. Pubmed, doi:10.1371/journal.pone.0152764.
Nagy E, Rodriguiz RM, Wetsel WC, MacIver NJ, Hale LP. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease. PLoS One. 2016;11(4):e0152764.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0152764

Location

United States

Related Subject Headings

  • Reproduction
  • Mice
  • Inflammatory Bowel Diseases
  • General Science & Technology
  • Disease Models, Animal
  • Animals