Anti-DTNA (aa 1-371) polyclonal antibody

DTNA encoding dystrobrevin-alpha (alpha-DB) is a putative causal gene associated with left ventricular noncompaction cardiomyopathy (LVNC). The aim of the study was to investigate the causal role of DTNA in LVNC using a transgenic mouse model. A missense mutation (c.146A > G, p.N49S) of DTNA was identified in a patient with LVNC by Sanger sequencing. Six independent lines of transgenic mice expressing the mutant DTNA under a myosin heavy chain 6 (Myh6) promoter were generated (Myh6:Dtna(N49S)). Phenotypic characteristics of DTNA-p.N49S mutations were evaluated by echocardiography, histological observation, and immunoblotting. Multiple trabeculation and a higher ratio of non-compacted to compact myocardial layer were found in the Myh6:Dtna(N49S) mice compared to the controls. The transgenic mice also showed left ventricular (LV) dilation and cardiac systolic dysfunction. In conclusion, overexpression of the DTNA-p.N49S mutation in a mouse heart can be responsible for the phenotype of deep trabeculation, dilated cardiomyopathy, and cardiac dysfunction, which resembles the phenotype of LVNC.

Dystrophin/dystrobrevin superfamily proteins play structural and signalling roles at the plasma membrane of many cell types. Defects in them or the associated multiprotein complex cause a range of neuromuscular disorders. Members of the dystrophin branch of the family form heterodimers with members of the dystrobrevin branch, mediated by their coiled-coil domains. To determine which combinations of these proteins might interact during embryonic development, we set out to characterise the gene expression pattern of dystrophin and dystrobrevin family members in zebrafish. gamma-dystrobrevin (dtng), a novel dystrobrevin recently identified in fish, is the predominant form of dystrobrevin in embryonic development. Dtng and dmd (dystrophin) have similar spatial and temporal expression patterns in muscle, where transcripts are localized to the ends of differentiated fibres at the somite borders. Dtng is expressed in the notochord while dmd is expressed in the chordo-neural hinge and then in floor plate and hypochord. In addition, dtng is dynamically expressed in rhombomeres 2 and 4-6 of the hindbrain and in the ventral midbrain. alpha-dystrobrevin (dtna) is expressed widely in the brain with particularly strong expression in the hypothalamus and the telencephalon; drp2 is also expressed widely in the brain. Utrophin expression is found in early pronephros and lateral line development and utrophin and dystrophin are both expressed later in the gut. beta-dystrobrevin (dtnb) is expressed in the pronephric duct and widely at low levels. In summary, we find clear instances of co-expression of dystrophin and dystrobrevin family members in muscle, brain and pronephric duct development and many examples of strong and specific expression of members of one family but not the other, an intriguing finding given the presumed heterodimeric state of these molecules. (c) 2007 Elsevier B.V. All rights reserved.