Altered neurological function in mice immunized with early endosome antigen 1.

Abstract

BACKGROUND: Autoantibodies directed against the 160 kDa endosome protein early endosome antigen 1 (EEA1) are seen in patients with neurological diseases. To determine if antibodies to EEA1 have a neuropathological effect, mice from three major histocompatibility haplotype backgrounds (H2q, H2b and H2d) were immunized with EEA1 (amino acids 82-1411) that was previously shown to contain the target EEA1 epitopes. The mice were then subjected to five neuro-behavioural tests: grid walking, forelimb strength, open field, reaching and rotarod. RESULTS: The immunized SWR/J mice with sustained anti-EEA1 antibodies had significantly reduced forelimb strength than the control non-immune mice of the same strain, and BALB/CJ immune mice demonstrated significantly more forelimb errors on the grid walk test than the control group. CONCLUSIONS: Antibodies to recombinant EEA1 in mice may mediate neurological deficits that are consistent with clinical features of some humans that spontaneously develop anti-EEA1 autoantibodies.