Human Disease Model Report: Emery-Dreifuss muscular dystrophy, LINC-complex-related

General Information

Name

Emery-Dreifuss muscular dystrophy, LINC-complex-related

FlyBase ID

FBhh0000812

Disease Ontology Term

Emery-Dreifuss muscular dystrophy

Parent Disease

OMIM

Overview

Many of the genes implicated in Emery-Dreifuss muscular dystrophy (EDMD) are part of or interact with the nuclear membrane LINC complex; for example, EMD (emerin), LMNA (lamin A/C), SYNE1 (nesprin 1), SYNE2 (nesprin 2), and TMEM43 (interacts with LINC complex within the nuclear membrane). Additional LINC complex members include SUN1 and SUN2.

Two Drosophila nesprins (Msp300 and klar) have been found to play roles in establishing and/or maintaining spacing of the multiple nuclei in larval muscle cells. Additional Drosophila genes that belong to gene families associated with members of the LINC complex have been characterized for effects upon muscle development, including bocks and Ote (emerins), and koi (orthologous to human SUN1 and SUN2). Animals homozygous for loss-of-function mutations of Ote and koi die during the embryonic stage. Larvae homozygous for loss-of-function mutations of Msp300, klar or bocks exhibit locomotor defects; at the cellular level, defects in positioning of nuclei and/or size of nuclei within larval muscle cells are observed.

See also the human disease model report 'muscular dystrophy, lamin-related' (FBhh0000196). Loss-of-function muscle phenotypes of Drosophila genes related to human genes associated with EDMD vs. genes associated centronuclear myopathy have been compared (see 'centronuclear myopathy, X-linked' FBhh0000394 and centronuclear myopathy 2 FBhh0000813).

[updated May 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: Emery-Dreifuss muscular dystrophy, LINC-complex-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

The LINC (linker of nucleoskeleton and cytoskeleton) complex resides within the nuclear membrane; it connects the nucleus to cytoskeletal filaments and performs diverse functions including nuclear positioning, mechanotransduction, and meiotic chromosome movements. The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the nuclear envelope and also with other binding partners, including actin filaments and B-type lamins. Besides its mechanotransduction functions, the LINC complex is also involved in signalling pathways and gene regulation. [Meinke, et al., 2011; pubmed:22103509; Chang et al., 2015; pubmed:25559183).

(FlyBase Curators, 2013-)

A number of genes implicated in Emery-Dreifuss muscular dystrophy are part of or interact with the nuclear membrane LINC complex, including EMD, LMNA, SYNE1, SYNE2, and TMEM43. [from MIM:300384, MIM:150330, MIM:608441, MIM:608442 and MIM:612048; 2018.05.24]

(OMIM, 2013-)

External links

Disease synonyms

Related Diseases

Related human health report(s)

muscle and aortic defects, ARIH1-related

muscular dystrophy, Emery-Dreifuss

muscular dystrophy, lamin-related

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (3)

Dmel\Msp300

Gene Snapshot

Muscle-specific protein 300 kDa (Msp300) encodes a Nesprin-like protein that is required for proper positioning of muscle nuclei, mitochondria, and neuromuscular junction. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

KASH

Comments on ortholog(s)

Low-scoring ortholog of SYNE1 and SYNE2; additional related genes in both species. Dmel\Msp300 shares 18-19% identity and 35% 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

H. sapiens (Human)

Dmel\klar

Gene Snapshot

klarsicht (klar) encodes a member of the Nesprin family that links microtubule motors and various cellular structures. It controls the migration and positioning of nuclei in photoreceptors and muscles. It also regulates the motion of RNP granules in oocytes and lipid droplets in embryos. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

KASH

Comments on ortholog(s)

Member of the nesprin gene family; no orthologous gene(s) 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)

Dmel\bocks

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Related to the emerin gene family (LEM-like domain superfamily); no orthologous gene(s) 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 (35 groups)

Msp300

protein-protein

Interacting group

Assay

References

Msp300 - Amph

anti bait coimmunoprecipitation, western blot

(Reuveny et al., 2018)

Msp300 - hts

proximity-dependent biotin identification, Identification by mass spectrometry

(Mannix et al., 2019)

Msp300 - kel

proximity-dependent biotin identification, Identification by mass spectrometry

(Mannix et al., 2019)

Msp300 - klar

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Ding et al., 2017, Elhanany-Tamir et al., 2012)

Msp300 - kud

anti tag coimmunoprecipitation, anti tag western blot

(Ding et al., 2017)

Msp300 - lwr

two hybrid

(Hu et al., 2017.6.13)

Msp300 - Rab2

pull down, peptide massfingerprinting

(Gillingham et al., 2014)

Msp300 - sls

anti bait coimmunoprecipitation, western blot

(Elhanany-Tamir et al., 2012)

RNA-protein

Interacting group

Assay

References

Msp300 - par-6

anti bait coimmunoprecipitation, primer specific pcr

(Packard et al., 2015)

Msp300 - Syp

anti tag coimmunoprecipitation, quantitative reverse transcription pcr, anti bait coimmunoprecipitation, fluorescence correlation spectroscopy

(Titlow et al., 2020, McDermott et al., 2014)

klar

protein-protein

Interacting group

Assay

References

klar - αTub84B

pull down, western blot

(Myat et al., 2015)

klar - αTub84D

pull down, western blot

(Myat et al., 2015)

klar - Khc

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation

(Gaspar et al., 2014)

klar - kud

anti tag coimmunoprecipitation, anti tag western blot

(Ding et al., 2017)

klar - Lsd-2

two hybrid

(Welte et al., 2005)

klar - Msp300

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Ding et al., 2017, Elhanany-Tamir et al., 2012)

klar - stau

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation

(Gaspar et al., 2014)

RNA-protein

Interacting group

Assay

References

klar - osk

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Gaspar et al., 2014)

bocks

protein-protein

Interacting group

Assay

References

bocks - baf

two hybrid

(Schulze et al., 2009, Pinto et al., 2008)

bocks - CG3548

experimental knowledge based

(Guruharsha et al., 2011)

bocks - dnk

experimental knowledge based

(Guruharsha et al., 2011)

bocks - fal

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Flad1

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Gnf1

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Hmgs

experimental knowledge based

(Guruharsha et al., 2011)

bocks - indra

experimental knowledge based

(Guruharsha et al., 2011)

bocks - JMJD6

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Lam

experimental knowledge based, two hybrid

(Guruharsha et al., 2011, Schulze et al., 2009)

bocks - LamC

two hybrid

(Schulze et al., 2009)

bocks - MAN1

two hybrid

(Pinto et al., 2008)

bocks - nwk

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Ote

experimental knowledge based

(Guruharsha et al., 2011)

bocks - prod

experimental knowledge based

(Guruharsha et al., 2011)

bocks - RPA2

experimental knowledge based

(Guruharsha et al., 2011)

bocks - Sumo

anti tag coimmunoprecipitation, comigration in sds page, anti tag western blot

(Pirone et al., 2017)

bocks - TFAM

experimental knowledge based

(Guruharsha et al., 2011)

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

Msp300

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Msp300^3prime

model of Emery-Dreifuss muscular dystrophy

CEA

(Wang et al., 2015)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Msp300^3prime

model of Emery-Dreifuss muscular dystrophy

is exacerbated by shot^SF20

(Wang et al., 2015)

klar

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

klar^Δ1-18

model of Emery-Dreifuss muscular dystrophy

CEA

(Wang et al., 2015)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

klar^YG3

ameliorates amyotrophic lateral sclerosis type 8

modeled by Vap33^{P58S.UAS.Tag:FLAG}

(Sanhueza et al., 2015)

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

klar^GD9271

P{GD9271}

w¹¹¹⁸; P{GD9271}v32836

klar^JF02944

P{TRiP.JF02944}

y¹ v¹; P{TRiP.JF02944}attP2 e¹

klar^HMS01612

P{TRiP.HMS01612}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01612}attP2

bocks^GD13812

P{GD13812}

w¹¹¹⁸; P{GD13812}v24189

y¹ v¹; P{TRiP.HMS01817}attP40

w¹¹¹⁸; P{GD8201}v17346

w¹¹¹⁸ P{GD10317}v50192

Msp300^GD10406

P{GD10406}

w¹¹¹⁸; P{GD10406}v25906

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00368}attP2

Msp300^HMS00632

P{TRiP.HMS00632}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00632}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

klar¹

loss of function allele

ru¹ klar¹ hry⁴¹ / TM3, y⁺ ru¹ klar¹ kni^ri-1 p^p vvl^sep Sb¹ Ubx^bx-34e e^s Ser¹

klar^marb-BX5

loss of function allele

X ray

klar^marb-BX5 st¹/TM6B, Tb¹

klar^marb-BX1

loss of function allele

X ray

klar^marb-BX15

loss of function allele

X ray

klar^marb-BX12

loss of function allele

X ray

klar^marb-FQ19

loss of function allele

ethyl methanesulfonate

klar^marb-BX7

loss of function allele

X ray

klar^marb-BX19

loss of function allele

X ray

klar^marb-BX14

loss of function allele

X ray

klar^marb-BX14 st¹

klar^marb-BX6

loss of function allele

X ray

klar^marb-BX4

loss of function allele

X ray

klar^marb-BX8

loss of function allele

X ray

klar^marb-BX2

loss of function allele

X ray

klar^marb-FU2

loss of function allele

ethyl methanesulfonate

klar^marb-BX16

loss of function allele

X ray

klar^marb-BX17

loss of function allele

X ray

klar^marb-BX21

loss of function allele

X ray

klar^marb-FN1

loss of function allele

ethyl methanesulfonate

klar^marb-BX11

loss of function allele

X ray

klar^marb-BX9

loss of function allele

X ray

klar^marb-BX3

loss of function allele

X ray

bw¹; klar^marb-BX3 st¹/TM6B, Tb¹

klar^marb-BX13

loss of function allele

X ray

klar^marb-BX20

loss of function allele

X ray

klar^marb-BX10

loss of function allele

X ray

klar^marb-BP

loss of function allele

Delta2-3 transposase

klar^marb-CD4

loss of function allele

ethyl methanesulfonate

w^*; bw¹; klar^marb-CD4 st¹/TM6B, Tb⁺

klar^YG3

P-element activity

klar^Δ1-18

amorphic allele - molecular evidence

FLPase

bocks^Δ10

amorphic allele - molecular evidence

Delta2-3 transposase

bocks^Δ66

amorphic allele - molecular evidence

Delta2-3 transposase

Msp300^sz75

loss of function allele

ethyl methanesulfonate

Msp300^3prime

References (12)

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