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

Abstract

27The present study is designed to identify the influences of genetic background to optic nerve 28 regeneration using the two parental strains C57BL/6J and DBA/2J and 7 BXD recombinant 29 inbred strains. To study regeneration in the optic nerve, Pten was knocked down in the retinal 30 ganglion cells using AAV, and a mild inflammatory response was induced by an intravitreal 31 injection of zymosan with CPT-cAMP, and the axons were damaged by optic nerve crush (ONC). 32Regenerating axons were labeled by Cholera Toxin B and quantified 14 days after ONC. The 33 number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we 34 measured the distance that 5 axons had grown down the nerve and the longest distance a single 35 axon reached. Results showed a considerable amount of differential axonal growth across all 9 36 BXD strains. There was a significant difference (P=0.014 Mann-Whitney U test) in the 37 regenerative capacity in the number of axons reaching 0.5 mm from a low of 1487.6 ± 264.9 38 axons in BXD102 to a high of 4175.8 ± 648.6 axons in BXD29. There were also significant 39 differences (P=0.014 Mann-Whitney U test) in the distance axons traveled, looking at a 40 minimum of 5 axons with the shortest distance was 787.2 ± 46.5µm in BXD102 to a maximum 41 distance of 2025.5 ± 223.3µm in BXD29. These results reveal that genetic background can 42 modulate axonal regeneration and that the BXD strains are a particularly well-suited model 43 system. 44 45 peer-reviewed)