This report describes muscular dystrophy, limb-girdle, autosomal dominant 2 (LGMDD2). The human gene implicated in this disease is TNPO3, a nuclear import receptor. There is a single orthologous gene in Drosophila, Tnpo-SR, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of human Hsap\TNPO3 have been introduced into flies, including wild-type and a variant implicated in this disease. The disease model combines tissue-specific RNAi-mediated knockdown of the fly Tnpo-SR gene with tissue-specific expression of the human gene carrying the disease-implicated variant. Hsap\TNPO3 variant expression in muscle or in motor neurons causes muscle atrophy in adult flies; reduced locomotor ability and reduced adult lifespan are observed. The efficacy of the drug chloroquine (FBch0000075) has been assessed in this model.
[updated Sep. 2021 by FlyBase; FBrf0222196]
[MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 2; LGMDD2](https://omim.org/entry/608423)
[TRANSPORTIN 3; TNPO3](https://omim.org/entry/610032)
Autosomal dominant limb-girdle muscular dystrophy-2 is a myopathy characterized by proximal muscle weakness primarily affecting the lower limbs, but also affecting the upper limbs in most patients. Affected individuals also have distal muscle weakness of the hands and lower leg muscles. There is variability in presentation and progression (summary by Melia et al., 2013; pubmed:23543484).[from MIM:608423; 2021.09.26]
Autosomal dominant limb-girdle muscular dystrophy-2 (LGMDD2) is caused by heterozygous mutation in the TNPO3 gene. [from MIM:608423; 2021.09.26]
Muscle biopsy shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and filamentous inclusions (summary by Melia et al., 2013; pubmed:23543484). [from MIM:608423; 2021.09.26]
TNPO3 (Transportin 3) encodes a nuclear import receptor for serine/arginine-rich (SR) proteins such as the splicing factors SFRS1 and SFRS2. The TNPO3 protein has also been shown to be involved in HIV-1 infection, apparently through interaction with the HIV-1 capsid protein. [Gene Cards, TNPO3; 2021.09.26]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human TNPO3 (1 Drosophila to 1 human).
