International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Wednesday 20 November

09:30 - 09:45 HRS

FUNCTIONAL AND MICROARRAY ANALYSIS OF KY, A TRANSGLUTAMINASE-LIKE PROTEIN UNDERLYING THE KYPHOSCOLIOTIC NEUROMUSCULAR DYSTROPHY IN THE MOUSE

G Blanco
MRC Harwell

Co-Authors: Wright E, Pritchard C, Brown SDM
Institutions: MGU and UK Mouse Genome Centre

The ky mouse mutant exhibits a primary degenerative myopathy preceding chronic thoraco-lumbar kyphoscoliosis and is encoded by a novel protein that belongs to the recently established family of transglutaminase-like proteins (Blanco et al., 2001 Hum. Mol. Genet. 10, 9). The histopathology of the ky mutant suggests that Ky protein activity is crucial for normal muscle growth and function as well as the maturation and stabilization of the neuromuscular junction. In vitro expression in muscle cells of a GFP tagged Ky suggests that it is a cytosolic protein. Full length Ky interacts in the two-hybrid system with the slow isoform of Myosin binding protein C, consistent with the fact the ky neuromuscular dystrophy affects primarily postural tonically active muscles affluent in slow type fibers. In order to profile the molecular changes caused by the absence of Ky and to shed light on the primary function of Ky, mouse 'known gene' oligo arrays have been used. The microarray results revealed the ky transcript amongst the top downregulated genes in ky soleus muscle. However, mitochondrial uncoupling protein 1(UCP1) and 2 (UCP2) are significantly upregulated in ky soleus muscle. UCP1 shows the highest difference and this upregulation has been confirmed on Westerns and by immunofluorescence experiments. Inappropriate expression of UCPs and consequent mitochondria uncoupling may be a primary molecular cause of the disease.


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