Deletion of the Casp8 gene in mice results in ileocolitis, gut barrier dysfunction and malassimilation, which can be partially attenuated by inulin or butyrate.

08:00 EDT 14th August 2019 | BioPortfolio

Summary of "Deletion of the Casp8 gene in mice results in ileocolitis, gut barrier dysfunction and malassimilation, which can be partially attenuated by inulin or butyrate."

Genetically modified mice have been successfully used as models for inflammatory bowel diseases; however, dietary effects were poorly examined. Here, we studied the effects of particular nutrients and supplements on gut functions related to the knockout of the epithelial caspase-8 gene. Casp8 knockout and control littermates were fed for 4 weeks a control diet (CD) enriched with 10% inulin (CD-Inu) or 5% butyrate (CD-But) while having free access to plain water or water supplemented with 30% fructose (+F). Body weight changes, intestinal inflammation, selected marker for barrier function, and markers of liver steatosis were assessed. Casp8 knockout mice developed ileocolitis accompanied by changes in intestinal barrier morphology and the expression of barrier-related genes such as mucin-2 ( and defensins in the ileum and in the colon. Casp8 knockout mice fed a control diet also showed impaired body weight gain compared to control mice, which was even more pronounced in mice receiving water supplemented with fructose. Furthermore, we observed pronounced liver steatosis and inflammation in some but not all Casp8 knockout mice under a control diet, which was in average similar to that observed in control mice under a fructose-rich diet. Hepatic lipid accumulation, as well as some markers of ileal barrier function, but not intestinal pathohistology or body weight loss, was attenuated by diets enriched with inulin or butyrate, especially in the absence of fructose supplementation. Our data show that ileocolitis, barrier dysfunction and malassimilation in Caspase-8 knockout mice can be partially attenuated by oral inulin or butyrate supplementation.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Gastrointestinal and liver physiology
ISSN: 1522-1547


DeepDyve research library

PubMed Articles [25969 Associated PubMed Articles listed on BioPortfolio]

Environmental Microbial Factors Determine the Pattern of Inflammatory Lesions in a Murine Model of Crohn's Disease-Like Inflammation.

Crohn's disease (CD) patients can be grouped into patients suffering from ileitis, ileocolitis, jejunoileitis, and colitis. The pathophysiological mechanism underlying this regional inflammation is st...

Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.

The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs)...

Ubiquitin Ligases cIAP1 and cIAP2 Limit Cell Death to Prevent Inflammation.

Cellular inhibitor of apoptosis proteins cIAP1 and cIAP2 ubiquitinate nuclear factor κB (NF-κB)-inducing kinase (NIK) to suppress non-canonical NF-κB signaling and substrates such as receptor inter...

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan.

Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contri...

Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice.

Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We test the hypothesis that oxidative stress plays a key role in the developme...

Clinical Trials [6664 Associated Clinical Trials listed on BioPortfolio]

Detection of IKZF1 Deletion Mutation in Patients With Acute Lymphoblastic Leukemia and Its Impact in Therapy

1. To detect IKZF-1 deletion mutations in patients with ALL. 2. To study the impact of IKZF-1 deletion mutation on therapy of ALL. 3. To study the correlation between IKZF-1 deletion...

Identification of Gene Polymorphism in Patients With Sick Sinus Syndrome in Chinese Population in Taiwan

Background: Sinus node dysfunction is a major cause of bradycardia necessitating pacemaker implantation. Evidences of genetic study supported that some genes involved in the pacemaker curr...

Genetics and Psychopathology in the 22q11 Deletion Syndrome

The purposes of this study are to: 1. study the nature and longitudinal course of psychiatric symptoms in children with the 22q11.2 deletion syndrome and 2. identify genes...

Protease Activated Receptor-2 and Gastrointestinal Dysfunction in Critical Illness

Gastrointestinal (GI) dysfunction affects up to 50% of medical and surgical critically ill children. GI dysfunction, specifically gastric dysmotility and loss of epithelial barrier integri...

Intestinal Barrier Function and Liver Cirrhosis

Patients with liver cirrhosis have an increased risk to develop life-threatening complications such as spontaneous bacterial peritonitis (SBP). Impairment in the intestinal barrier, change...

Medical and Biotech [MESH] Definitions

A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.

A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

A fibroblast growth factor that may play a role in regulation of HAIR FOLLICLE phenotype. Spontaneous mutation of the gene for this protein results in a strain of MICE with abnormally long hair, referred to as angora mice.

Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.

Quick Search

DeepDyve research library

Relevant Topics

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article