Human Disease Model Report: inflammatory bowel disease, tight/septate junction defect

General Information

Name

inflammatory bowel disease, tight/septate junction defect

FlyBase ID

FBhh0000256

Disease Ontology Term

inflammatory bowel disease

Parent Disease

OMIM

Overview

Inflammatory bowel disease (IBD) represents a group of intestinal disorders that cause prolonged inflammation of the digestive tract. This report describes work in Drosophila that associates defects in septate junctions (functionally analogous to tight junctions in vertebrates) with abnormal activation of the gut immune response, chronic gut epithelial inflammation and reduced longevity when exposed to oral bacterial infections. Multiple aspects of this system are similar to the chronic gut epithelial inflammation observed for human inflammatory bowel diseases.

Mutations in the Drosophila gene bbg, which is associated with septate junctions, have been the most extensively characterized. There is no gene orthologous to bbg in humans. RNAi directed against the fly gene cora, which belongs to a family of plasma membrane-associated cytoplasmic proteins known to be associated with septate junctions, results in a similar phenotype of reduction in survival upon oral bacterial infection.

The Drosophila Ssk gene encodes an occluding junction protein which is critical for the proper formation of invertebrate smooth septate junctions; there is no gene orthologous to Ssk in humans. Loss of Ssk leads to rapid and reversible intestinal barrier dysfunction, altered gut morphology, dysbiosis, and dramatically reduced lifespan. Intestinal up-regulation of Ssk protects against microbial infection, improves intestinal barrier function during aging, limits dysbiosis, and extends lifespan.

[updated May 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: inflammatory bowel disease, tight/septate junction defect

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of the digestive tract. IBD primarily includes ulcerative colitis and Crohn's disease. Both usually involve severe diarrhea, pain, fatigue and weight loss. IBD can be debilitating and sometimes leads to life-threatening complications. (http://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/basics/definition/con-20034908; 2016.09.14)

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

External links

KEGG Disease Pathways: Inflammatory bowel disease (IBD)
NCBI MedGen: Inflammatory bowel disease

Disease synonyms

inflammatory bowel disease (postulated), tight/septate junction defect

Search term: intestinal barrier dysfunction

Related Diseases

Related human health report(s)

inflammatory bowel disease

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (3)

Dmel\cora

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human genes EPB41L3, EPB41L2, EPB41L1, and EPB41 (1 Drosophila to 4 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\bbg

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Ssk

Gene Snapshot

Snakeskin (Ssk) encodes an occluding junction protein which, along with its counterpart Tetraspanin 2A (Tsp2A) and the cell adhesion protein mesh, is critical for the proper formation of invertebrate smooth septate junctions. Ssk shows highly enriched expression in the Malpighian (renal) tubules, midgut, and hindgut. [Date last reviewed: 2023-11-16]

Molecular function (GO)

protein binding

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

No orthologous gene has been identified in human.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (27 groups)

cora

protein-protein

Interacting group

Assay

References

cora - Dg

anti tag coimmunoprecipitation, western blot

(Bogdanik et al., 2008)

cora - foxo

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cora - ft

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

cora - gig

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cora - Gli

anti tag coimmunoprecipitation, western blot

(Schulte et al., 2006)

cora - GluRIIA

two hybrid

(Chen et al., 2005)

cora - GluRIIC

two hybrid

(Chen et al., 2005)

cora - GluRIID

two hybrid

(Chen et al., 2005)

cora - kel

proximity-dependent biotin identification, Identification by mass spectrometry

(Mannix et al., 2019)

cora - Nrg

anti bait coimmunoprecipitation, western blot

(Genova and Fehon, 2003)

cora - nrv1

anti bait coimmunoprecipitation, western blot

(Genova and Fehon, 2003)

cora - nrv2

anti bait coimmunoprecipitation, western blot

(Genova and Fehon, 2003)

cora - Nrx-IV

anti bait coimmunoprecipitation, western blot

(Genova and Fehon, 2003)

cora - rictor

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cora - S6kII

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cora - sima

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cora - Tctp

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down, molecular weight estimation by staining

(Lee et al., 2020)

cora - Tsc1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

RNA-RNA

Interacting group

Assay

References

cora - mir-184

immunohistochemistry, luminiscence technology

(Sharifkhodaei et al., 2016, Kertesz et al., 2007)

RNA-protein

Interacting group

Assay

References

cora - stau

anti tag coimmunoprecipitation, reverse transcription pcr

(Song et al., 2022)

bbg

protein-protein

Interacting group

Assay

References

bbg - cher

anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot

(Külshammer et al., 2022)

bbg - kst

two hybrid, anti tag coimmunoprecipitation, anti tag western blot

(Forest et al., 2018)

bbg - sqh

anti tag coimmunoprecipitation, western blot

(Tsoumpekos et al., 2018)

Ssk

protein-protein

Interacting group

Assay

References

Ssk - hoka

anti bait coimmunoprecipitation, western blot

(Izumi et al., 2021)

Ssk - mesh

anti bait coimmunoprecipitation, western blot

(Izumi et al., 2021, Izumi et al., 2012)

Ssk - Tsp2A

anti tag coimmunoprecipitation, western blot

(Izumi et al., 2016)

Ssk - yki

anti tag coimmunoprecipitation, anti tag western blot

(Chen et al., 2020)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

cora

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

cora^GD1405

model of inflammatory bowel disease

CEA

(Bonnay et al., 2013)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

cora¹⁴

ameliorates Huntington's disease

modeled by Hsap\HTT^{128Q.1-231.UAS}

(Onur et al., 2021)

bbg

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

bbg^EY02818

model of inflammatory bowel disease

CEA with bbg^B211

(Bonnay et al., 2013)

bbg^B211

model of inflammatory bowel disease

CEA

(Bonnay et al., 2013)

CEA with bbg^EY02818

(Bonnay et al., 2013)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

bbg^EY08296

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

bbg^EY21339

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Ssk^GD4623

P{GD4623}

w¹¹¹⁸; P{GD4623}v11906

w¹¹¹⁸; P{GD1405}v9787

y¹ v¹; P{TRiP.HM05144}attP2/TM3, Sb¹

cora^HMS01413

P{TRiP.HMS01413}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01413}attP2

cora^HMC03418

P{TRiP.HMC03418}

y¹ v¹; P{TRiP.HMC03418}attP40

bbg^HMJ23903

P{TRiP.HMJ23903}

y¹ v¹; P{TRiP.HMJ23903}attP40/CyO

bbg^GD6101

P{GD6101}

w¹¹¹⁸; P{GD6101}v15975

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

cora^jc

amorphic allele - molecular evidence

CRISPR/Cas9

cora¹

loss of function allele

cora²

loss of function allele

y¹ w^*; P{y.FRT.GAL4}52B cora²/CyO

cora⁵

loss of function allele

ethyl methanesulfonate

w^*; P{neoFRT}43D cora⁵/CyO

cora¹⁴

ethyl methanesulfonate

P{neoFRT}43D cora¹⁴/CyO

bbg^EY02818

amorphic allele - molecular evidence

P-element activity

y¹ w^67c23; P{EPgy2}bbg^EY02818/TM3, Sb¹, Ser¹

bbg^B211

P-element activity

w^*; P{5'GawB}bbg^B211

bbg^EY08296

y¹ w^67c23; P{EPgy2}bbg^EY08296

bbg^EY21339

y¹ w^67c23; P{EPgy2}bbg^EY21339

References (7)

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