Kell and XK immunohistochemistry in McLeod myopathy.
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.
Jung
H H
HH
Department of Neurology, University Hospital Zürich, 8091 Zürich, Switzerland. hans.jung@nos.usz.ch
Russo
D
D
Redman
C
C
Brandner
S
S
D026921:Amino Acid Transport Systems, Neutral; D001706:Biopsy; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007626:Kell Blood-Group System / Q000235:genetics*; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology*
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D007626:Kell Blood-Group System; D008565:Membrane Proteins; C087883:XK protein, human