Disease relevance of Col6a1

• We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy [1].

High impact information on Col6a1

• We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis [1].
• Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo [1].
• Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis [1].
• The data configure the -5.4/-3.9 region of the Col6a1 gene as a new type of tissue-specific enhancer, characterized by a variety of tissues supporting its activation and by the dependence of its function only on ubiquitous transcription factors [2].
• The results indicate that regulation of transcription of the Col6a1 gene by different cis-acting elements (core promoter, AP1 binding site and enhancers) is not completely modular, but the final output depends on the specific interactions among the three elements in a defined cell type [3].

Other interactions of Col6a1

• With fiber-FISH, Col18a1, Col6a1, and Col6a2 were shown to be in a head-to-tail configuration with respective intergenic distances of about 350 kb and 90 kb [4].

Analytical, diagnostic and therapeutic context of Col6a1

• The function of the AP1 binding site and of the core promoter in the transcriptional regulation of the Col6a1 gene was investigated by expressing several promoter-reporter gene constructs in transgenic mice and in cell cultures [3].

References