FlyBase Allele Report: Dmel\LamC[R205W.UAS]

General Information

Symbol

Dmel\LamC^R205W.UAS

Species

D. melanogaster

Name

FlyBase ID

FBal0347191

Feature type

allele

Associated gene

Dmel\LamC

Associated Insertion(s)

Carried in Construct

P{UAS-LamC.R205W}

Also Known As

R205W

Key Links

Genomic Maps

JBrowse

Transgenic product class

missense_variant

(Shaw et al., 2022, Bhide et al., 2018)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Shaw et al., 2022, Bhide et al., 2018)

Mutagen

in vitro construct

(Bhide et al., 2018)

Progenitor genotype

Carried in construct

P{UAS-LamC.R205W}

Cytology

Description

UASt regulates expression of R205W LamC, modeling the R190W mutation in human Hsap\LMNA associated with muscular dystrophy.

(Shaw et al., 2022)

UASt regulatory sequences drive expression of LamC containing the amino acid replacement R205W (this is equivalent to a R190W mutation in the human Hsap\LMNA gene, a variant that is associated with cardiac defects).

(Bhide et al., 2018)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

LamC

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

2R:14,572,634..14,572,636 [-]

Nucleotide change:

CGC14572636TGG

Reported nucleotide change:

CGC>TGG

Reported nucleotide change:

CGC?TGG

Amino acid change:

R205W | LamC-PA; R205W | LamC-PB

Reported amino acid change:

R205W

Comment:

Analogous R190W mutation in human LMNA implicated in dilated cardiomyopathy 1A; mutation carried on in vitro construct.

Comment:

Analogous R190W mutation in human LMNA implicated in muscular dystrophy, lamin-related; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.

(Miao et al., 2022, Bhide et al., 2018)

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Chandran et al., 2019)

model of dilated cardiomyopathy 1A

CEC

(Shaw et al., 2022, Bhide et al., 2018)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

Comments on Models/Modifiers Based on Experimental Evidence ( 1 )

FlyBase curator comment: "dilated cardiomyopathy 1A" is associated with mutations in human LMNA.

(Bhide et al., 2018)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Shaw et al., 2022, Bhide et al., 2018)

LMNA:p.Arg190Trp

(FlyBase curators, 2019-)

Variants Synonym(s)

LMNA:p.Arg78Trp

LMNA:p.Arg109Trp

Associated human disease model(s)

dilated cardiomyopathy 1A

External database links

ClinVar: LMNA_66908

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal flight, with Scer\GAL4^EDTP-DJ694

(Chandran et al., 2019)

abnormal size | adult stage, with Scer\GAL4^Act88F.PB

(Chandran et al., 2019)

abnormal size | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

flightless | progressive, with LamC^EX296, Scer\GAL4^fln.IFM

(Chandran et al., 2019)

flightless | progressive, with Scer\GAL4^Act88F.PB

(Chandran et al., 2019)

flightless | progressive, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

lethal - all die before end of P-stage, with Scer\GAL4^C57

(Shaw et al., 2022)

short lived, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

Phenotype Manifest In

adult abdominal fat mass, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

adult heart | progressive, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

embryonic/larval hypodermal muscle | larval stage, with Scer\GAL4^C57

(Shaw et al., 2022)

indirect flight muscle cell | adult stage, with Scer\GAL4^EDTP-DJ694

(Chandran et al., 2019)

indirect flight muscle cell | adult stage | progressive, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

indirect flight muscle cell | pupal stage, with Scer\GAL4^Act88F.PB

(Chandran et al., 2019)

lipid droplet | adult stage, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

mitochondrion | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

myofibril | adult stage, with Scer\GAL4^EDTP-DJ694

(Chandran et al., 2019)

myofibril | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

myofibril | adult stage, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

nuclear envelope | adult stage, with Scer\GAL4^EDTP-DJ694

(Chandran et al., 2019)

nuclear envelope | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

nuclear envelope | adult stage, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

nucleus | adult stage, with Scer\GAL4^EDTP-DJ694

(Chandran et al., 2019)

nucleus | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

nucleus | adult stage, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

sarcomere | adult stage, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

sarcomere | pupal stage | pupal stage, with Scer\GAL4^Act88F.PB

(Chandran et al., 2019)

wing, with Scer\GAL4^fln.IFM

(Chandran et al., 2019)

Z disc | adult stage, with Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

Detailed Description

Statement

Reference

The expression of LamC^R205W.UAS under the control of Scer\GAL4^fln.IFM or Scer\GAL4^Act88F.PB leads to a severe and progressive decrease in flight ability, until individuals are unable to fly; expression under the control of Scer\GAL4^EDTP-DJ694 leads to a milder decrease in flight ability; the Scer\GAL4^fln.IFM-driven flight defects are also observed in a LamC^EX296 heterozygous background.

Expressing LamC^R205W.UAS under the control of Scer\GAL4^Act88F.PB leads to structural defects in pupal indirect flight muscles, with shorter sarcomeres, and disrupted Z-discs and M-lines.

Adult indirect flight muscles expressing LamC^R205W.UAS under the control of either Scer\GAL4^fln.IFM or Scer\GAL4^EDTP-DJ694 show myofibril disorganization and abnormal nuclear morphology, including nuclear envelope blebbing. The Scer\GAL4^fln.IFM-driven expression also leads to shorter sarcomeres, with partial loss of Z-disc and M-lines, to severe mitochondrial dysmorphology including small and fragmented mitochondria, and to double membrane structures containing mitochondria and vacuoles, suggesting autophagic defects; adults show a nearly fully penetrant 'held-up wing' phenotype.

(Chandran et al., 2019)

Expressing LamC^R205W.UAS under the control of Scer\GAL4^HCH.Hand causes cardiac defects: 3 weeks adults show significant dilation, defective ostia, dysrhythmic beating, non-beating segments and non-beating hearts; there are progressive increases in heart period, diastolic and systolic intervals, a progressive decrease in fractional shortening, and a significant increase in diastolic arrhythmicity index. In 3-week-old adults, cardiomyocytes show myofibrillar disorganization and poorly organized Z-discs and nuclear envelope blebbing; the fat body exhibits enlarged lipid droplets.

(Bhide et al., 2018)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressed by

Statement

Reference

LamC^R205W.UAS, Scer\GAL4^HCH.Hand has short lived phenotype, suppressible | partially by Atg1^UAS.cSa, Scer\GAL4^HCH.Hand

(Bhide et al., 2018)

NOT suppressed by