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The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene.

Luna-Sánchez M, Díaz-Casado E, Barca E, Tejada MÁ, Montilla-García Á, Cobos EJ, Escames G, Acuña-Castroviejo D, Quinzii CM, López LC - EMBO Mol Med (2015)

Bottom Line: Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis.The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear.Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain Centro de Investigación Biomédica, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.

No MeSH data available.


Related in: MedlinePlus

Female Coq9Q95X mice develop a mild myopathic phenotype with exercise intoleranceA–C Voluntary wheel running test. Distance traveled on the wheel and average speed during the use of the wheel were decreased in female Coq9Q95X mice at 6 months of age (B, C).D Hanging wire test. Coq9Q95X female mice obtained less reaches score in the ‘fall and reaches’ method.E Open-field test. Coq9Q95X mice showed a reduction in the average distance traveled in Coq9Q95X female mice at 6 months of age.F Grip test: Muscle strength was not affected in Coq9Q95X mice at 6 months of age.Data information: Data are expressed as mean ± SD. Statistical analysis was performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ females versus Coq9Q95X females. *P < 0.05; **P < 0.01 and ***P < 0.001. Student's t-test. n = 8 for each group.
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fig09: Female Coq9Q95X mice develop a mild myopathic phenotype with exercise intoleranceA–C Voluntary wheel running test. Distance traveled on the wheel and average speed during the use of the wheel were decreased in female Coq9Q95X mice at 6 months of age (B, C).D Hanging wire test. Coq9Q95X female mice obtained less reaches score in the ‘fall and reaches’ method.E Open-field test. Coq9Q95X mice showed a reduction in the average distance traveled in Coq9Q95X female mice at 6 months of age.F Grip test: Muscle strength was not affected in Coq9Q95X mice at 6 months of age.Data information: Data are expressed as mean ± SD. Statistical analysis was performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ females versus Coq9Q95X females. *P < 0.05; **P < 0.01 and ***P < 0.001. Student's t-test. n = 8 for each group.

Mentions: Because the muscle was the most impaired tissue in Coq9Q95X homozygous mice, we assessed the locomotor activity and muscle strength at 6 months of age. Compared to sex-matched wild-type controls, Coq9Q95X females showed a significant reduction on the average speed during the use of the wheel and spontaneous wheel activity, while there were no differences between mutant and control male animals (Fig9A–C). The decrease in the distance travelled in the home-cage running wheels was corroborated by the observation of reduced spontaneous movement in the open-field test (Fig9E). Likewise, the reaches score obtained in the hanging wire test was lower just in homozygous mutant females (Fig9D). However, muscle strength of forelimbs was not affected (Fig9F). The life span of Coq9Q95X and Coq9+/+ mice was similar in both genders.


The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene.

Luna-Sánchez M, Díaz-Casado E, Barca E, Tejada MÁ, Montilla-García Á, Cobos EJ, Escames G, Acuña-Castroviejo D, Quinzii CM, López LC - EMBO Mol Med (2015)

Female Coq9Q95X mice develop a mild myopathic phenotype with exercise intoleranceA–C Voluntary wheel running test. Distance traveled on the wheel and average speed during the use of the wheel were decreased in female Coq9Q95X mice at 6 months of age (B, C).D Hanging wire test. Coq9Q95X female mice obtained less reaches score in the ‘fall and reaches’ method.E Open-field test. Coq9Q95X mice showed a reduction in the average distance traveled in Coq9Q95X female mice at 6 months of age.F Grip test: Muscle strength was not affected in Coq9Q95X mice at 6 months of age.Data information: Data are expressed as mean ± SD. Statistical analysis was performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ females versus Coq9Q95X females. *P < 0.05; **P < 0.01 and ***P < 0.001. Student's t-test. n = 8 for each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492823&req=5

fig09: Female Coq9Q95X mice develop a mild myopathic phenotype with exercise intoleranceA–C Voluntary wheel running test. Distance traveled on the wheel and average speed during the use of the wheel were decreased in female Coq9Q95X mice at 6 months of age (B, C).D Hanging wire test. Coq9Q95X female mice obtained less reaches score in the ‘fall and reaches’ method.E Open-field test. Coq9Q95X mice showed a reduction in the average distance traveled in Coq9Q95X female mice at 6 months of age.F Grip test: Muscle strength was not affected in Coq9Q95X mice at 6 months of age.Data information: Data are expressed as mean ± SD. Statistical analysis was performed on Coq9+/+ male mice versus Coq9Q95X male mice and Coq9+/+ females versus Coq9Q95X females. *P < 0.05; **P < 0.01 and ***P < 0.001. Student's t-test. n = 8 for each group.
Mentions: Because the muscle was the most impaired tissue in Coq9Q95X homozygous mice, we assessed the locomotor activity and muscle strength at 6 months of age. Compared to sex-matched wild-type controls, Coq9Q95X females showed a significant reduction on the average speed during the use of the wheel and spontaneous wheel activity, while there were no differences between mutant and control male animals (Fig9A–C). The decrease in the distance travelled in the home-cage running wheels was corroborated by the observation of reduced spontaneous movement in the open-field test (Fig9E). Likewise, the reaches score obtained in the hanging wire test was lower just in homozygous mutant females (Fig9D). However, muscle strength of forelimbs was not affected (Fig9F). The life span of Coq9Q95X and Coq9+/+ mice was similar in both genders.

Bottom Line: Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis.The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear.Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain Centro de Investigación Biomédica, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.

No MeSH data available.


Related in: MedlinePlus