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January 1, 2026Human Molecular GeneticsOpen Access

Camk2b overexpression enhances oxidative metabolism and functional performance in calpain 3 knockout muscles.

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Why the study?

To investigate the contribution of CaMKIIbeta signaling to the calpain 3-deficient phenotype in limb girdle muscular dystrophy R1.

Does overexpression of constitutively active CaMK2b improve oxidative metabolism and functional performance in calpain 3 knockout models of LGMDR1?

Population

Camk2b cKO mice, C3KO mice, and LGMDR1 patient biopsies

Comparison

Loss-of-function and gain-of-function CaMK2b models

Design

Preclinical animal and human biopsy study

Key result

Overexpression of constitutively active Camk2b in calpain 3 knockout muscles enhanced oxidative metabolism and improved functional performance, highlighting its therapeutic potential for LGMDR1.

Authors

IKIrina KramerovaFAFrieda AnastopulosDBDiana Becerra

Discussion

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Member takes

Overview

May improve metabolic outcomes in LGMDR1 models; leaves open translation of CaMKIIβ targeting to patients.

Structured PICO

Does overexpression of constitutively active CaMK2b improve oxidative metabolism and functional performance in calpain 3 knockout models of LGMDR1?

P
Population
Mouse models (calpain 3 knockout [C3KO], muscle-specific conditional knockout of Camk2b [Camk2b cKO]) and LGMDR1 patient biopsies
I
Intervention
Muscle-specific overexpression of a constitutively active CaMK2b
C
Comparator
C3KO muscles without overexpression (implied)
O
Outcome
Oxidative metabolism gene expression and functional performancesurrogate

Blunted CaMKIIβ signaling contributes to metabolic insufficiency in LGMDR1, and targeting this pathway may ameliorate disease features.

Cite This Study

Kramerova et al. (2026) studied Limb girdle muscular dystrophy R1 (LGMDR1). Loss-of-function (Camk2b cKO) and gain-of-function (overexpression of constitutively active CaMK2b) vs. C3KO muscles / wild-type was evaluated on Muscle phenotype, oxidative metabolism, and functional performance. Overexpression of constitutively active Camk2b in calpain 3 knockout muscles enhanced oxidative metabolism and improved functional performance, highlighting its therapeutic potential for LGMDR1.

synapsesocial.com/papers/6aa85d941199070892aa92cfhttps://doi.org/10.1093/hmg/ddag090
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Attenuated Ca2+ release in a mouse model of limb girdle muscular dystrophy 2A2016 · 18 citations
  2. 2Mitochondrial dysfunction and consequences in calpain-3-deficient muscle2020 · 22 citations
  3. 3Targeted inhibition of Ca2+/calmodulin signaling exacerbates the dystrophic phenotype in mdx mouse muscle2006 · 64 citations
  4. 4Mitochondrial CaMKII causes adverse metabolic reprogramming and dilated cardiomyopathy2020 · 93 citations
  5. 5CaMKII content affects contractile, but not mitochondrial, characteristics in regenerating skeletal muscle2014 · 28 citations