| First Author | Wu G | Year | 2009 |
| Journal | Biochim Biophys Acta | Volume | 1791 |
| Issue | 5 | Pages | 347-56 |
| PubMed ID | 19236939 | Mgi Jnum | J:164859 |
| Mgi Id | MGI:4835402 | Doi | 10.1016/j.bbalip.2009.02.006 |
| Citation | Wu G, et al. (2009) Understanding the muscular dystrophy caused by deletion of choline kinase beta in mice. Biochim Biophys Acta 1791(5):347-56 |
| abstractText | 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. |
