BOX 3-1
The Story of Nogo-Knockout Mice: Cooperation, Collaboration, and Genetic Variability

Three groups of investigators recently used the gene-knockout strategy to examine whether Nogo, a potential inhibitor of axon growth (see Chapter 2), was responsible for preventing neuronal regeneration after an injury (Steward et al., 2003). Researchers coordinated their research efforts and published their findings in papers published in the same issue of the journal. Each group removed a specific part of a mouse’s chromosome that is responsible for Nogo, with the hypothesis that if Nogo is responsible for inhibiting neurons from growing, then its removal would facilitate regeneration after a spinal cord injury. However, the experiments found contradictory results. One study reported that the loss of Nogo increased the extent of neuronal regeneration, as predicted (but only in young mice), and the second study reported a more modest enhancement; however, the third group did not find any significant difference (Kim et al., 2003; Simonen et al., 2003; Zheng et al., 2003). The various results could have been due to differences in the ages and the genetic backgrounds of the mice, the strategy used to delete the Nogo gene, and the compensatory changes in other genes. In order to better understand the differences in these results, two of the groups have set up a collaboration to share their mice and perform their own analyses. This example demonstrates the value of genetic techniques, the importance of consistency in experimental design, the need to replicate experimental results, and the value of collaborative and collegial interactions between research groups.

well understood). In amphibians, regeneration readily occurs directly through the glial scar.

Different strains of the same animal species may respond differently to spinal cord trauma. For example, the nature and the extent of the secondary injury and wound healing vary in different strains of mice (Inman et al., 2002). Although these differences in responses between strains and species complicate comparison of the results of studies with different animal species, they may provide important insights about the specific genes that affect postinjury signaling cascades (Inman et al., 2002). Furthermore, the differences observed in experiments with the Nogo gene (Box 3-1) provide important lessons about the necessity to replicate experiments.

Scale

The human spinal cord is more than four times as long as the rat’s entire CNS (brain and spinal cord). Figure 3-1 demonstrates the difference in size between the entire CNS of a rat and the caudal end of a human spinal cord. A contusion or transection trauma in humans can affect upwards of 2 to 3 centimeters of the spinal cord, which is approximately 10



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