Understanding the muscular dystrophy caused by deletion of choline kinase beta in mice.
Cells-Cultured, Choline-Kinase, Creatine-Kinase, Cytidine-Diphosphate-Choline, Gene-Deletion, Hindlimb, Insulin-Like-Growth-Factor-I, Mice, Mitochondria, Muscles, Muscular-Dystrophies, Myoblasts, Myostatin, Phosphatidylcholines, Proliferating-Cell-Nuclear-Antigen, Receptors-Lipoprotein, Regeneration, Substrate-Specificity
Biochim Biophys Acta 2009 May; 1791(5):347-56.
Choline kinase in mice is encoded by two genes, Chka and Chkb. Disruption of murine Chka leads to embryonic lethality, whereas a spontaneously occurring genomic deletion in murine Chkb results in neonatal bone deformity and hindlimb muscular dystrophy. We have investigated the mechanism by which a lack of choline kinase beta, encoded by Chkb, causes hindlimb muscular dystrophy. The biosynthesis of phosphatidylcholine (PC) is impaired in the hindlimbs of Chkb -/- mice, with an accumulation of choline and decreased amount of phosphocholine. The activity of CTP: phosphocholine cytidylyltransferase is also decreased in the hindlimb muscle of mutant mice. Concomitantly, the activities of PC phospholipase C and phospholipase A2 are increased. The mitochondria in Chkb -/- mice are abnormally large and exhibit decreased inner membrane potential. Despite the muscular dystrophy in Chkb -/- mice, we observed increased expression of insulin like growth factor 1 and proliferating cell nuclear antigen. However, regeneration of hindlimb muscles of Chkb -/- mice was impaired when challenged with cardiotoxin. Injection of CDP-choline increased PC content of hindlimb muscle and decreased creatine kinase activity in plasma of Chkb -/- mice. We conclude that the hindlimb muscular dystrophy in Chkb -/- mice is due to attenuated PC biosynthesis and enhanced catabolism of PC.
Wu, G; Sher, R B.; Cox, G A.; and Vance, D E., "Understanding the muscular dystrophy caused by deletion of choline kinase beta in mice." (2009). Faculty Research 2000 - 2009. 2054.