| Title: |
JAK3-deficient mini-pigs exhibit impaired lymphoid organogenesis, intestinal structure, and leukocyte/cytokine production |
| Authors: |
Jeong, PS; Yang, HJ; Park, YH; Jin, YB; Song, BS; Hong, JJ; Lee, SH; Lee, JH; Lim, KS; Jeong, KJ; Kang, P; Lee, HY; Son, HC; Kim, HN; Ha, SM; Hwang, EH; Cha, JJ; Jung, Y; Choi, SA; Lee, S; Lee, SR; Lee, SC; Kang, KS; Hur, CG; Jung, YW; Koo, DB; Choo, YK; Kim, JM; Sim, BW; Kim, SU |
| Contributors: |
113862; Lee, SR |
| Publication Year: |
2026 |
| Subject Terms: |
Animals; Cytokines; Disease Models; Animal; Gene Knockout Techniques; Humans; Intestines; Janus Kinase 3; Leukocytes; Lymphoid Tissue; Organogenesis; Severe Combined Immunodeficiency; Swine; Miniature; Intestinal mucosal structure; JAK3; Lymphoid organogenesis; Macrophage activation; Severe combined immunodeficiency mini-pig model |
| Description: |
INTRODUCTION: Severe combined immunodeficiency (SCID) mini-pigs are a highly versatile model for human disease research and regenerative medicine. OBJECTIVES: This study aims to generate a novel JAK3-deficient mini-pig model with a human-like immune system and to elucidate how JAK3 plays an important role in immune system. METHODS: JAK3 and RAG2 knockout (KO) mini-pigs were generated using CRISPR/Cas9 and somatic cell nuclear transfer. These mini-pigs were transferred to a sterilized isolator within a specific pathogen-free facility. Phenotypic characteristics and clinical manifestations were analyzed through histological and hematological analysis of SCID mini-pigs to explore the unique role of JAK3 in immune functions. RESULTS: JAK3 KO was characterized by defects in T and NK cells, very low levels of B cells, and a complete absence of thymus and lymph nodes. Notably, JAK3 KO mini-pigs had significantly reduced numbers of monocytes in peripheral blood, macrophages in tissue, and inflammatory cytokines, suggesting that JAK3 KO can induce a broad immunodeficiency that extends to the myeloid system as well as the lymphoid. Moreover, JAK3 KO mini-pigs had intestinal abnormalities similar to those of patients. CONCLUSION: These results suggest that JAK3 KO mini-pigs can be used as an effective model for the development of therapies for SCID patients, as well as for regenerative medicine applications such as the development of patient-specific artificial organs. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
J020901232; http://repository.ajou.ac.kr/handle/201003/34913; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869250 |
| DOI: |
10.1016/j.jare.2025.04.036 |
| Availability: |
http://repository.ajou.ac.kr/handle/201003/34913; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869250; https://doi.org/10.1016/j.jare.2025.04.036 |
| Accession Number: |
edsbas.F2CD8B67 |
| Database: |
BASE |