FB2024_03 , released June 25, 2024
Allele: Dmel\MhcR146N
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General Information
Symbol
Dmel\MhcR146N
Species
D. melanogaster
Name
FlyBase ID
FBal0343874
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Genomic Maps

Transgenic product class
Nature of the Allele
Transgenic product class
Progenitor genotype
Carried in construct
Cytology
Description

A Mhc transgene carrying an amino acid substitution equivalent to the K146N (dominant) mutation in human beta-cardiac myosin heavy chain that causes hypertrophic cardiomyopathy. (FlyBase curator comment: the mutation in the Mhc gene is given as R146N in FBrf0240086, however analysis of the release 6.32 annotated gene model indicates the change to be R147N).

Allele components
Component
Use(s)
Regulatory region(s)
Encoded product / tool
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Nucleotide change:

CG16770547AA

Reported nucleotide change:

CGC>AAC

Amino acid change:

R147N | Mhc-PA; R147N | Mhc-PB; R147N | Mhc-PC; R147N | Mhc-PD; R147N | Mhc-PE; R147N | Mhc-PF; R147N | Mhc-PG; R147N | Mhc-PH; R147N | Mhc-PI; R147N | Mhc-PK; R147N | Mhc-PL; R147N | Mhc-PM; R147N | Mhc-PN; R147N | Mhc-PO; R147N | Mhc-PP; R147N | Mhc-PQ; R147N | Mhc-PR; R147N | Mhc-PS; R147N | Mhc-PT; R147N | Mhc-PU; R147N | Mhc-PV

Reported amino acid change:

R146N

Comment:

Analogous K146N mutation in human MYH7 implicated in hypertrophic cardiomyopathy; mutation carried on in vitro construct.

Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

The disease model uses Mhc[R146N] in either a Mhc[10]/Mhc[10] or Mhc[1]/+ background.

Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.
MYH7:p.Lys146Asn
Variants Synonym(s)
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Indirect flight muscles in Mhc10/Mhc10, MhcR146N/MhcR146N females show normal sarcomere organization at late pupal stage and in 2h-old adults, minor disruptions of thick and thin filament packing in 2-days old adults, and disorder in myofibril morphology in 7-days old adults, including gaps in the hexagonal packing of thick and thin filaments and disruption in the Z- and M-lines, as compared to controls. These muscles also show significantly decreased power generation and work, significantly increased active tension, but do not show a significant change in passive tension, as compared to controls; under optimal power producing conditions, there are further significant decreases in power generation, net work (likely due to decreased work generated:work absorbed ratio), and in relative muscle length amplitude, as compared to controls. These muscle defects are associated with a progressive decrease in flight index and a lower wing beat frequency, as compared to controls. Mhc10/Mhc10, MhcR146N/+ individuals display similar, albeit more modest, flight ability defects and indirect flight muscle morphology and performance defects.

The hearts of Mhc10/Mhc10, MhcR146N/+ individuals display significant decreases in cardiac dimensions (diastolic and systolic diameters) and in fractional shortening, and a significant increase in systolic interval, but do change in heart period, as compared to controls; the heart has an essentially normal myofibrillar integrity and organization in 1-week old adults, but displays myofibrillar discontinuities in 3-weeks old adults, as compared to controls; cardiomyocyte thickness in both young and aged mutant adults shows no statistically significant differences, as compared to controls.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Comments
Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (1)
Reported As
Symbol Synonym
MhcR146N
Name Synonyms
Secondary FlyBase IDs
    References (2)