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. 2015 Jun 19;22(9):1402–1412. doi: 10.1038/cdd.2015.65

Table 2. Summary of findings of genetic manipulations of calcium handling in transgenic used to investigate mechanisms of MD pathology.

Genetic alteration Year Dystrophy model Change in calcium handling Change in phenotype
Sarcolemma
 dn TRPC6 transgenic81 2009 mdx and Sgcd−/− dnTRPC6 inhibited increased SOCE in Sgcd−/− fibers dnTRPC6 TG reduced histopathology and serum CK
 Trpc3 overexpression81 2009 Trpc3 transgenic Increased SOCE versus WT TRPC3 TG caused dystrophy-like histopathology without membrane permeability
 Adenoviral dnTRPV288 2008 Bio14.6 hamster Decreased calcium influx in high-calcium solution dnTRVP2 decreased dystrophic histopathology
 Transgenic dnTRPV288 2008 mdx Decreased calcium influx in high-calcium with 2-APB dnTPV2 improved muscle function and decreased histopathology
 Trpv2−/−89 2009 mdx Not evaluated Trpv2−/− had increased force and decreased membrane permeability
 Stim1 transgenic87 2014 Stim1 transgenic Stim1 overexpression increased SOCE and resting calcium Stim1 TG led to severe dystrophy-like phenotype in muscle
 dnOrai1 Tg87 2014 mdx and Sgcd−/− dnOrai inhibited increased SOCE in Sgcd−/− and mdx fibers dnOrai TG decreased histopathology and CK release in muscle
 NCX1 Tg33 2014 mdx, Sgcd−/−, and Dysf−/− NCX1 increased [Na]i and increased Na, Ca exchange NCX1 TG worsened pathology in hindlimb but improved pathology in diaphragm
 Slc8a1f/f with MLC-CRE33 2014 Sgcd−/− Not evaluated Deletion of NCX1 protein improved histopathology at early time points
         
EC-coupling
 SERCA1 transgenic15 2011 Sgcd−/− and mdx SERCA1 increased rate of SR-calcium uptake SERCA1 TG decreased histopathology and serum CK
 SERCA1 transgenic15 2011 TRPC3 Not evaluated SERCA1 TG rescued pathology mediated by TRPC3 overexpression.
 AAV-SERCA215 2011 mdx Not evaluated SERCA2a overexpression improved histopathology in gastrocnemius
 AAV-SERCA147 2010 mdx Not evaluated SERCA1 improved force after eccentric contraction and decreased histopathology
         
Mitochondrial
 Ppif−/−109 2008 mdx, Sgcd−/− and Lama2 Ppif deletion decreased mitochondrial swelling Ppif−/− decreased histopathology in all MD models. Improved strength in Sgcd−/−
 Ppif−/−110 2009 Col6a1−/− Ppif deletion decreased mitochondrial depolarization Ppif−/− decreased histopathology and EBD uptake
         
Calpain
 Calpastatin transgenic23 2002 mdx Not evaluated Calpastatin overexpression decreased histopathology and EBD uptake