Evidence that Pax7 contains two polymorphic homeoboxes, one of which has a rearrangement associated with enhanced skeletal muscle regrowth
Fletcher, S., Kay, P.H., Harmon, D., Robertson, T. and Papadimitriou, J.M. (1997) Evidence that Pax7 contains two polymorphic homeoboxes, one of which has a rearrangement associated with enhanced skeletal muscle regrowth. In: XIII International Congress of Neuropathology, 7 - 12 September 1997, Perth, Australia.
Understanding of the genetic control of myogenesis has been advanced by the identification of many different types of skeletal muscle forming genes which are active during development. Members of the basic helix-loop-helix (bH-L-H) gene family encode proteins involved in the terminal pathway of skeletal muscle differentiation. A further set of developmental genes characterised by the presence of a paired box and a homeobox are involved in myogenesis at an earlier stage of skeletal muscle development.
Pax7 is a paired type homeobox gene which has been shown to play an important role in the formation of skeletal muscle in the developing embryo. Recently, rearrangement of the homeobox of a Pax7-like gene was shown to be associated with enhanced skeletal muscle regrowth in injured mice. Evidence has now been found indicating that Pax7 is associated with two polymorphic homeoboxes which identify four different Pax7 allotypes.
Genomic DNA from inbred laboratory mouse strains was examined for structural variation of Pax7 following digestion with Taql. When the Southern blots were hybridised with Pax7 homeobox-specific sub-probes, two polymorphic fragments were identified in all samples other than from MBK mice. For further evidence that the Pax7 gene contains two homeoboxes, genomic DNA from BALB/C, C3WHeJ, SJL/J and DDO mice was digested with Taql and separated on a 1% agarose gel. The regions of agarose containing the fragments hybridising with the homeobox specific probe were excised from the gel. The DNA was recovered and used as target in a PCR with primers specific for a 67bp region of the homeobox.
Functional studies on laboratory mice with different allotypic forms of Pax7 have shown that enhanced skeletal muscle regrowth is completely associated with the presence of a Taql site in one of the two Pax7 homeoboxes.
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