The influence of muscle type and dystrophin deficiency on murine expression profiles


Haslett JN, Kang PB, Han M, Kho AT, Sanoudou D, Volinski JM, Beggs AH, Kohane IS, Kunkel LM. The influence of muscle type and dystrophin deficiency on murine expression profiles. Mamm GenomeMamm GenomeMamm Genome. 2005;16:739-48.


The phenotypic differences among Duchenne muscular dystrophy patients, mdx mice, and mdx(5cv) mice suggest that despite the common etiology of dystrophin deficiency, secondary mechanisms have a substantial influence on phenotypic severity. The differential response of various skeletal muscles to dystrophin deficiency supports this hypothesis. To explore these differences, gene expression profiles were generated from duplicate RNA targets extracted from six different skeletal muscles (diaphragm, soleus, gastrocnemius, quadriceps, tibialis anterior, and extensor digitorum longus) from wild-type, mdx, and mdx(5cv) mice, resulting in 36 data sets for 18 muscle samples. The data sets were compared in three different ways: (1) among wild-type samples only, (2) among all 36 data sets, and (3) between strains for each muscle type. The molecular profiles of soleus and diaphragm separate significantly from the other four muscle types and from each other. Fiber-type proportions can explain some of these differences. These variations in wild-type gene expression profiles may also reflect biomechanical differences known to exist among skeletal muscles. Further exploration of the genes that most distinguish these muscles may help explain the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin deficiency.


Haslett, Judith NKang, Peter BHan, MeiKho, Alvin TSanoudou, DespinaVolinski, Jay MBeggs, Alan HKohane, Isaac SKunkel, Louis MengR01 AR44349/AR/NIAMS NIH HHS/P50 NS040828/NS/NINDS NIH HHS/P01 NS40828-01A1/NS/NINDS NIH HHS/K08 NS048180/NS/NINDS NIH HHS/U01 HL066582-01/HL/NHLBI NIH HHS/Comparative StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.2005/11/02 09:00Mamm Genome. 2005 Oct;16(10):739-48. doi: 10.1007/s00335-005-0053-8. Epub 2005 Oct 29.