Human Disease Model Report: insulin pathway effects, BMP/TGFB-related

General Information

Name

insulin pathway effects, BMP/TGFB-related

FlyBase ID

FBhh0000531

Disease Ontology Term

glucose metabolism disease

Parent Disease

OMIM

Overview

Adult flies fed a high-fat diet (HFD) develop a number of phenotypes associated with type-2 diabetes, including elevated triglyceride and circulating glucose levels, and insulin resistance (see FBhh0000530). Under these conditions, it has been observed that expression of the gene gbb is elevated. Under normal dietary conditions, overexpression of gbb in the fat body produces phenotypes similar to those of HFD-fed flies. In HFD-fed flies, reduced levels of gbb effected by RNAi result in amelioration of the HFD-induced metabolic phenotypes.

Dmel\gbb is a member of the TGFbeta superfamily; there are many members of this family in both human and flies. The human genes most closely related to gbb are BMP7, BMP6, BMP5, BMP8A and BMP8B. One of these genes, Hsap\BMP7, has been introduced into flies. Heterologous rescue (functional complementation) is observed: when expression from the Dmel\gbb promoter, the wild-type Hsap\BMP7 gene is able to rescue the visible phenotype of a gbb loss-of-function mutation.

Animals homozygous for amorphic mutations of Dmel\gbb die during the larval stage; as larvae, they exhibit neurophysiology and neuroanatomy defects. Physical and genetic interactions of gbb have been described; see below and in the gbb gene report.

[updated Apr. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: insulin pathway effects, BMP/TGFB-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

BMP6 is associated with body fat distribution in a GWAS study (see GWAS Catalog, below in 'External links').

(FlyBase Curators, 2013-)

BMP5 is associated with Obesity-related traits in a GWAS study (see GWAS Catalog, below in 'External links').

(FlyBase Curators, 2013-)

Cellular phenotype and pathology

Molecular information

The TGFbeta superfamily is a large family of related growth factors comprised of at least 30 members in mammals; members play key roles throughout development and in adult homeostatic processes (reviewed in Weiss and Attisano, 2013; pubmed:23799630).

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): BMP7 bone morphogenetic protein 7
Gene Cards: BMP7 gene
Gene Cards: BMP7 bone morphogenetic protein 7
MedlinePlus (genomic research): Genome-wide association studies
GWAS Catalog: BMP5
GWAS Catalog: BMP6
MARRVEL (human gene): BMP7 bone morphogenetic protein 7
NCBI (Entrez) gene: BMP7 bone morphogenetic protein 7

Disease synonyms

Related Diseases

Related human health report(s)

diabetes mellitus, noninsulin-dependent (type 2) (fly models overview)

insulin signaling, regulation of fat storage, Drosophila fat body model

Ortholog Information

Human gene(s) in FlyBase

Hsap\BMP7

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\gbb

Gene Snapshot

glass bottom boat (gbb) encodes a BMP ligand in the TGF-beta/BMP family of dimeric signaling molecules. It binds to a receptor complex to transduce signal through phosphorylation of the product of Mad. It contributes to maintain stem cell populations, control cell fate specification, proliferation, synapse growth and neuropeptide release. [Date last reviewed: 2018-09-20]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Many to many; multiple paralogous and orthologous genes in both human and flies. The human genes most closely related to gbb are BMP7, BMP6, BMP5, BMP8A and BMP8B.

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 (15 groups)

gbb

protein-protein

Interacting group

Assay

References

gbb

chromatography technology, western blot, coimmunoprecipitation, comigration in non denaturing gel electrophoresis

(Anderson and Wharton, 2017)

gbb - cmpy

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, two hybrid

(James et al., 2014, James and Broihier, 2011)

gbb - ctrip

anti tag coimmunoprecipitation, anti tag western blot

(Hossain et al., 2023)

gbb - cv

anti tag coimmunoprecipitation, anti tag western blot

(Shimmi et al., 2005)

gbb - cv-2

anti tag coimmunoprecipitation, anti tag western blot

(Serpe et al., 2008)

gbb - cv-d

anti tag coimmunoprecipitation, anti tag western blot

(Chen et al., 2012)

gbb - dpp

anti tag coimmunoprecipitation, anti tag western blot, comigration in non denaturing gel electrophoresis, western blot

(Anderson and Wharton, 2017, Tian and Jiang, 2014, Serpe et al., 2005)

gbb - GstO1

anti tag coimmunoprecipitation, western blot

(Hossain et al., 2023)

gbb - Hsap\FURIN

enzymatic study, western blot

(Anderson and Wharton, 2017)

gbb - nord

anti tag coimmunoprecipitation, anti tag western blot

(Yang et al., 2022)

gbb - sax

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Akiyama et al., 2012, Le and Wharton, 2012, Haerry, 2010)

gbb - sog

anti tag coimmunoprecipitation, anti tag western blot

(Shimmi et al., 2005)

gbb - stj

proximity ligation assay, fluorescence microscopy

(Hoover et al., 2019)

gbb - tkv

anti tag coimmunoprecipitation, anti tag western blot

(Haerry, 2010)

gbb - tsg

anti tag coimmunoprecipitation, anti tag western blot

(Shimmi et al., 2005)

Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)

gbb

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

gbb^UAS.cKa

model of fibrodysplasia ossificans progressiva

CEA with sax^{K262H.UAS.Tag:FLAG}

(Le et al., 2018)

model of obesity

CEA

(Hong et al., 2016)

model of diabetes mellitus

CEA

(Hong et al., 2016)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

gbb¹

ameliorates Huntington's disease

modeled by Hsap\HTT^{Q138.UAS.mRFP1}

(Akbergenova and Littleton, 2017)

gbb²

ameliorates Huntington's disease

modeled by Hsap\HTT^{Q138.UAS.mRFP1}

(Akbergenova and Littleton, 2017)

gbb^UAS.cKa

ameliorates amyotrophic lateral sclerosis type 1

modeled by Sod1^G85R

(Held et al., 2019)

model of obesity

is ameliorated by trbl^RNAi.UAS.cUa

(Hong et al., 2016)

model of diabetes mellitus

is ameliorated by trbl^RNAi.UAS.cUa

(Hong et al., 2016)

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

gbb^UAS.cKa

P{UAS-gbb.K}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01243}attP2

gbb^NIG.5562R

P{NIG.5562R}

P{NIG.5562R}1

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

gbb²

amorphic allele - genetic evidence

gbb¹

loss of function allele

bw¹ gbb¹/SM6a

References (5)

Report Sections

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