Spontaneous development of autoimmune diseases in H165A mice. (A and B) Joint swellings of a forepaw and a hindpaw (A) and histology (B) of 21-wk-old H165A and BALB/c mice. Scale bar: 3 mm in A, 200 μm in B. (C) Arthritis incidences (left) and scores (right) for BALB/c, H165A, W163C (SKG), and W163A mice (n = 27 each). (D and E) Histological (D) and macroscopic views (E) of the colon from H165A and BALB/c mice. Scale bar: 10 μm in D, 10 mm in E. (F) Frequency of diarrheic mice in BALB/c and ZAP-70 mutant strains (n = 32 each). (G) Serum levels of indicated antibodies in BALB/c, SKG, H165A, and W163A mice. (H) Arthritis scores after transfer of 1 × 10⁶ CD4⁺ T cells from BALB/c, H165A, SKG, or W163A mice into RAG2^−/− mice (n = 7 each). (I) Arthritis scores after mannan treatment of SKG, H165A, W163A, and BALB/c mice. Mean ± SD in C, H, and I. Two-tailed unpaired Student’s t test (G). *P < 0.05; **P < 0.005; ***P < 0.0005.