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This long-term single group pre/post-test design study was conducted with pre-service special education elementary teachers taking the graduate level course Integrating Technology in Mathematics and Science Instruction in Special Education and Inclusive Classrooms in a New York City public college. The purpose of this study was to a) analyze effect of the TPACK-based course on four domains of TPACK framework: TK, PK, CK (in math and science) and TPACK, and b) explore whether TK, PK, CK and TPACK are independent domains in TPACK framework. The paired sample t-test showed significant gains in teachers' TK, CK, and TPACK, however, there were no significant changes in PK. Confirmatory factor analysis suggests that TPACK domain is independent from TK, PK, and CK.