Objective To establish Sdpr-gene-knockout and Sdpr transgenic mouse models to provide suitable models for studying Sdpr gene function. Methods Sdpr-knockout mice were constructed by CRISPR/ Cas9 technology, while Sdpr transgenic mice were constructed using plasmid overexpression. We identified mouse genotypes by PCR. The mRNA and protein expression levels were determined by qRT-PCR and Western blot. Mouse tissues were obtained for histopathological analysis. We analyzed the immune cells of the knockout mice and transgenic mice by flow cytometry. Results Sdpr-gene-knockout and transgenic mouse models were obtained. Compared with that in the wild-type mice, the Sdpr gene expression level was decreased in the knockout mice. Meanwhile, inflammatory foci appeared in many tissues, such as inflammatory cells infiltrated into the lungs and fat. Hepatic steatosis can be observed, and extramedullary hematopoiesis can be seen around the central hepatic vein. Extramedullary hematopoiesis can be observed in the red pulp of the spleen. The proportion of T cells in bone marrow of the knockout mice decreased, the number of CD4^-CD8^- T cells in the thymus increased, while CD4⁺CD8⁺ T cells decreased. In terms of the findings in the transgenic mice, the expression level of the Sdpr gene increased. In addition, their liver cells showed slight fatty degeneration and widening of alveolar septa. Moreover, spleen lymphocytes exhibited hyperplasia and red pulp cells increased. The proportion of B cells in the peripheral blood of the transgenic mice increased while the proportions of myeloid and T cells decreased. Finally, thymus CD4⁺ T cells increased while CD4⁺ CD8⁺ T cells decreased. Conclusions Sdpr-knockout and transgenic mice were successfully established and identified, which can provide models for studying the mechanisms of action of Sdpr protein and its related caveolin protein in different tissues and organs.