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FB2026_03
,
released September 17, 2026
In humans, multiple genes have been implicated in muscular dystrophy (MD); this report describes a fly model of muscular dystrophy using the fly gene tn, which is related to the human gene TRIM32. TRIM32 is an E3 ubiquitin ligase that is implicated in a specific form of MD, limb-girdle muscular dystrophy type 2H (LGMD2H). There are multiple related genes in both humans and flies. Although Dmel\tn is the best orthologous hit to human TRIM32, it is not a reciprocal best hit; there are several other genes in humans that are better scoring orthologs of Dmel\tn. There are classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis available for tn.
The human TRIM32 gene has not been introduced into flies.
Amorphic mutations of Dmel\tn are lethal, typically during the pupal stage. Hatching occurs late and second/third instar molt is delayed. Third instar larvae are long, thin, and slow-moving; histological examination shows abnormal muscle structure. Puparia are also long and thin. Genetic and physical interactions have been described; see below and in the gene report for tn.
[updated Mar. 2016 by FlyBase; FBrf0222196]
Limb-girdle muscular dystrophy type 2H (LGMD2H) is a slowly progressive proximal muscular dystrophy. This form of MD is rare; it was originally described in a Hutterite population in Manitoba, Canada, and has since been found is some European populations. [from MIM:254110; 2016.03.28]
Autosomal recessive limb-girdle muscular dystrophy type 2H (LGMD2H) is caused by mutation in the gene encoding tripartite motif-containing protein-32 (TRIM32). [from MIM:254110; 2016.03.16]
The TRIM32 protein is a zinc-binding RING-finger ubiquitin (E3) ligase. In addition to the RING finger domain, the TRIM (tripartite) motif also includes a B-box type 1 and a B-box type 2, and a coiled-coil region.
Many to many: both humans and flies have multiple genes in this family; Dmel\tn is the best orthologous hit for human TRIM32, however this fly gene has several better-scoring orthologous genes in humans.
Low- to moderate-scoring homolog of human genes TRIM2 (reciprocal best hit) and TRIM3; lower-scoring ortholog of multiple other human TRIM genes, including TRIM32 (multiple Drosophila to multiple human). Dmel\tn is a larger protein with a central region that does not appear in the human proteins; it shares 27-39% identity and 42-57% similarity with orthologous human genes within the carboxy TRIM domain; it shares 23-24% identity and 40-44% similarity within a conserved amino region.