FB2025_01 , released February 20, 2025
Human Disease Model Report: cardiac function, response to hypoxia
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General Information
Name
cardiac function, response to hypoxia
FlyBase ID
FBhh0001182
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a Drosophila system for assessing response and recovery of the heart in conditions of hypoxia. Responses of wild-type flies and flies carrying a mutation in the sima gene have been compared. Dmel\sima encodes a transcription factor that plays a key role in the cellular response to hypoxia in flies. There are several genes orthologous to sima in human: HIF1A, EPAS1 (also known as HIF2A), and HIF3A. Heart physiology and function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, have also been characterized.

UAS constructs of the wild-type human Hsap\HIF1A gene have been introduced into flies, but have not been characterized in the context of this disease model.

Cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation were assessed in wild-type flies and flies homozygous for a loss-of-function allele of sima. Hearts from wild-type flies recovered quickly after acute hypoxia, however, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies carrying a sima loss-of-function allele exhibited exaggerated reductions in cardiac output in response to hypoxia.

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cardiac function, response to hypoxia
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

In human, hypoxia inducible factors HIF1A and HIF2A belong to a group of transcription factors which mediate most of the cellular responses to hypoxia at a transcriptional level, in tissues throughout the body (Abe et al., 2017; pubmed:28757538).

In the human heart, gene expression is adjusted to oxygen availability by several mechanisms, including regulation of gene transcription by the hypoxia-inducible basic helix-loop-helix transcription factor HIF1A (Giordano, 2005; pubmed:15765131).

External links
    Disease synonyms
    Ortholog Information
    Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human HIF1A, HIF3A, and EPAS1 (1 Drosophila to 3 human). Dmel\sima shares 28-29% identity and 44-47% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (197 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti bait coimmunoprecipitation, western blot
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        pull down, autoradiography, two hybrid
        anti tag coimmunoprecipitation, Identification by mass spectrometry
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        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        pull down, autoradiography
        anti tag coimmunoprecipitation, Identification by mass spectrometry
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        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        anti tag coimmunoprecipitation, western blot, two hybrid
        anti tag coimmunoprecipitation, Identification by mass spectrometry
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        affinity technology, fluorescence technology, predetermined participant
        anti tag coimmunoprecipitation, Identification by mass spectrometry
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        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
        Models Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 4 )
        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
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (4)