Kinesin Family Member 20B is Upregulated in a Murine Peripheral Nerve Injury Model

Objectives Kinesin Family Member 20B (KIF20B) is a cytokinesis-involved motor protein.[1] We have previously shown that antibodies directed against KIF20B (anti-KIF20B) are associated with cranial and peripheral neuropathies in systemic lupus erythematosus (SLE).[2,3] In the central nervous system, KIF20B is essential for normal cortical development in mice;[1] however, the role of KIF20B in the peripheral nervous system has not been explored. The aim of this study was to assess changes in KIF20B expression in a murine model of peripheral nerve injury. Methods Right sciatic nerve crush injury was performed in male and female C57BL/6 mice (young, age 2 months, n=4; old, 16 months, n=3) on day 0, with euthanasia and bilateral sciatic nerve collection on day 7. Spatial transcriptomics with single cell resolution was performed on both ipsilateral (injured) and contralateral (non-injured) nerves (Xenium, 10x Genomic, Pleasonton, CA, USA). Cells expressing KIF20B were labeled as positive. Chi-square tests were used to compare the proportion of KIF20B positive cells between injured and non-injured nerves, as well as between the nerve segments proximal and distal to the site of injury. Study protocol was approved by the University of Calgary Animal Ethics Committee. Results When KIF20B expression was compared across all cell types between injured and non-injured nerves, there was significantly greater expression in injured nerves (2.87%) when compared to non-injured nerves (0.83%; p=0.0000011), (Figure 1). In injured nerves, the proportion of KIF20B expressing cells was significantly increased in the segment distal to site of injury (3.51%) when compared to the proximal segment (1.28%; p=0.000000003), (Figure 1). There was no significant difference in KIF20B expression between non-injured nerves and the proximal segment of injured nerves (proximal, 1.28%; non-injured, 0.83%; p=0.16); (Figure 1). When KIF20B expression was assessed in individual cell types between injured and uninjured nerves, the greatest difference was seen in Schwann cells (injured, 4.90%; non-injured, 1.00%; p=0.0000087). There were no significant differences in KIF20B expression when old and young mice were compared. Figure 1: KIF20B expression in ipsilateral (injured) and contralateral (non-injured) mouse nerves in both young (2 months) and old (16 months) mice. KIF20B expression (yellow and teal squares) was increased distal to the site of injury in both young and old mice in the ipsilateral nerve when compared to the proximal segment, as well as the contralateral nerve. Nuclei (DAPI stain) denoted by blue dots, Boundary Protein Stain (ATP1A1) denoted by purple dots. D, distal; P, proximal. Conclusion KIF20B expression is increased in the distal segment of mouse sciatic nerves following crush injury and these changes are greatest in Schwann cells. Future studies are needed to characterize how Schwann cell expressed KIF20B contributes to peripheral nerve healing, as well as how anti-KIF20B antibodies might disrupt this process and potentially contribute to cranial and peripheral neuropathies in SLE. References [1.] Janisch K. Development 2013;140:4672-82. [2.] Krustev E. Lupus Sci Med 2024. [3.] Krustev E. Arthritis Rheumatol 2021;73:703-6.