The BXD Mouse Strains are a Model System for Studying Optic Nerve Regeneration

Abstract The present study is designed to identify the influences of genetic background to optic nerve regeneration using the two parental strains C57BL/6J and DBA/2J and 7 BXD recombinant inbred strains. To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using AAV, and a mild inflammatory response was induced by an intravitreal injection of zymosan with CPT-cAMP, and the axons were damaged by optic nerve crush (ONC). Regenerating axons were labeled by Cholera Toxin B and quantified 14 days after ONC. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that 5 axons had grown down the nerve and the longest distance a single axon reached. Results showed a considerable amount of differential axonal growth across all 9 BXD strains. There was a significant difference (P=0.014 Mann-Whitney U test) in the regenerative capacity in the number of axons reaching 0.5 mm from a low of 1487.6 ± 264.9 axons in BXD102 to a high of 4175.8 ± 648.6 axons in BXD29. There were also significant differences (P=0.014 Mann-Whitney U test) in the distance axons traveled, looking at a minimum of 5 axons with the shortest distance was 787.2 ± 46.5μm in BXD102 to a maximum distance of 2025.5 ± 223.3μm in BXD29. These results reveal that genetic background can modulate axonal regeneration and that the BXD strains are a particularly well-suited model system.