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FB2026_01
,
released March 12, 2026
This report describes amyotrophic lateral sclerosis 21 (ALS21), which is a subtype of amyotrophic lateral sclerosis; ALS21 exhibits autosomal dominant inheritance. The human gene implicated in this disease is MATR3, which encodes an RNA-binding nuclear matrix protein. There is no close ortholog of MATR3 in Drosophila.
Multiple UAS constructs of the human Hsap\MATR3 gene have been introduced into flies, including wild-type MATR3, genes carrying mutational lesions implicated in ALS21, and genes with deletions of postulated functional domains. Variant(s) implicated in human disease tested (as transgenic human gene, MATR): the S85C, F115C, and T622A variant forms of the human gene have been introduced into flies.
Targeted expression of Hsap\MATR3 in Drosophila muscles or motor neurons results in shortened lifespan and produces progressive motor defects, muscle degeneration and atrophy. Expression of Hsap\MATR3 carrying the S85C or F115C variant produce stronger and more deleterious phenotypes. Deletion of the RRM2 RNA-recognition domain mitigates the overexpression phenotypes. A genotype producing a mild wing phenotype was used to carry out a genetic screen for modifiers of the Hsap\MATR3 phenotypes.
[updated Jan. 2021 by FlyBase; FBrf0222196]
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from MIM:105400, 2015.02.11]
[AMYOTROPHIC LATERAL SCLEROSIS 21; ALS21](https://omim.org/entry/606070)
[MATRIN 3; MATR3](https://omim.org/entry/164015)
A characteristic feature of this disease is weakness of the vocal cords and throat, leading to weakness and changes in the voice; can result in difficulty swallowing (dysphagia). [from MedlinePlus, Distal myopathy 2; 2020.10.18]
Amyotrophic lateral sclerosis-21 is an autosomal dominant neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia (summary by Johnson et al., 2014; pubmed:24686783). [from MIM:606070; 2020.10.18]
Amyotrophic lateral sclerosis-21 (ALS21) is caused by heterozygous mutation in the matrin-3 gene (MATR3). [from MIM:606070; 2020.10.18]
The MATR3 protein is described as an RNA-binding nuclear matrix protein [MedlinePlus, MATR3; 2020.10.18]
MATR3 encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network; may play a role in nuclear retention of defective RNAs. [from Gene Cards, MATR3; 2020.10.18]
There is only a distantly related gene in Drosophila (heph) and it is more closely related to other human genes.