The McLeod syndrome is an X-linked neuroacanthocytosis manifesting with myopathy 
and progressive chorea. It is caused by mutations of the XK gene encoding the XK 
protein, a putative membrane transport protein of yet unknown function. In 
erythroid tissues, XK forms a functional complex with the Kell glycoprotein. 
Here, we present an immunohistochemical study in skeletal muscle of normal 
controls and a McLeod patient with a XK gene point mutation (C977T) using 
affinity-purified antibodies against XK and Kell proteins. Histological 
examination of the affected muscle revealed the typical pattern of McLeod 
myopathy including type 2 fiber atrophy. In control muscles, Kell 
immunohistochemistry stained sarcoplasmic membranes. XK immunohistochemistry 
resulted in a type 2 fiber-specific intracellular staining that was most 
probably confined to the sarcoplasmic reticulum. In contrast, there was only a 
weak background signal without a specific staining pattern for XK and Kell in 
the McLeod muscle. Our results demonstrate that the lack of physiological XK 
expression correlates to the type 2 fiber atrophy in McLeod myopathy, and 
suggest that the XK protein represents a crucial factor for the maintenance of 
normal muscle structure and function.