The theme of this week's presentation and journal club will be the genetic, molecular, and cellular bases of the muscular dystrophies. Some of the major issues to be discussed will concern questions that are directly relevant to virtually all neurodegenerative diseases:

Molecular pathogenesis: Are all muscular dystrophies, regardless of genetic basis, the 'same' disease?  Are there shared pathogenetic mechanisms that lead to the same outcome, a muscular dystrophy (and what exactly IS a muscular dystrophy?)

Selective vulnerability: Why are muscles preferentially affected by gene defects that are present in a wide variety of cell types? Why are specific muscles affected and others spared when the genetic and biochemical defect is present in all muscle cells?

Genotype/Phenotype relationships:  Why is it that different mutations in the same gene can lead to vastly different phenotypes?  Why is it that the same mutation, in the same family, can lead to different phenotypes?

The papers for presentation by Ann Nakayama and Jim Weimannwill be:

Grady RM, Grange RW, Lau KS, Maimone MM, Nichol MC, Stull JT, Sanes JR (1999) Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nat Cell Biol, 1: 215-220.

Hack AA, Ly CT, Jiang F, Clendenin CJ, Sigrist KS, Wollmann RL, McNally EM (1998) Gamma-sarcoglycan deficiency leads to muscle membrane defects and apoptosis independent of dystrophin. J Cell Biol, 142: 1279-1287.