Objectives: 

We have generated two targeted mouse lines; 1) a LacZ reporter line to study the exact location and 2) a null line lacking any collagen XIII expression to study biological function of the transmembrane collagen XIII, also found as a shed, soluble protein.

Methods and results: 

Beta-galactosidase marker stainings showed that collagen XIII is highly expressed postsynaptically at the neuromuscular junction (NMJ). The endplate structure in homozygous mice in both lines lacking intact collagen XIII was smaller and more fragmented than that seen in controls. These structural changes were accompanied by an electrophysiologically measurable defect in nerve conduction study. Structural and functional defects of the NMJ had impact on mouse weight, behaviour and general condition. Mice developed myopathy at old age, but yet the structure of NMJs was more disturbed in young than in old mice. It was found that postnatal maturation of the postsynaptic apparatus was delayed and the alignment of pre- and postsynaptic portions was incomplete at some junctions. Recombinant extracellular fragment of collagen XIII had in vitro a minor effect on presynaptic differentiation of motoneurons, but it speeded up the postsynaptic maturation on cultured myotubes.

Conclusions: 

These studies thus indicate that collagen XIII contributes to stabilization of the NMJ structure and promotes postsynaptic maturation, and this may occur in an autocrine fashion.