Measuring nerve regeneration in the mouse

Abstract

Genetic engineering of mice has become a major tool in understanding the roles of individual molecules in regeneration of nerves, and will play an increasing role in the future. Mice are in many ways well suited to assessment both of nerve regeneration after axotomy and of collateral sprouting of intact fibers into areas of denervation. However, mouse models present special challenges because of their small size, their inherent capacity for regeneration, and the potential strain effects. The most widely used model of regeneration, sciatic nerve injury, has its inherent limitations, and there is a need for other models of injury to long nerves. Measures of regeneration in the mouse can be divided into those that assess the latency to initiate growth, those sensitive to the rate of growth and the proportion of fibers growing at fast rates, those that assess the time to reinnervation of specific targets and the completeness of reinnervation, and those that assess specificity of reinnervation and functional recovery. The short length of nerve available in the mouse limits measures of the rates of outgrowth, and thus introduces a greater potential for "noise" of measurement than is seen in larger animals such as the rat. For both regeneration of interrupted fibers and collateral regeneration from intact fibers histological and physiological measures of "time to target" have the advantages of direct correlation with restoration of function, the ability to assess regeneration of different fiber types efficiently, and the fact that most of these measures are easier in the mouse than in the rat.