PMID- 34179719
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240402
IS  - 2576-2095 (Electronic)
IS  - 2096-5451 (Print)
IS  - 2576-2095 (Linking)
VI  - 4
IP  - 2
DP  - 2021 Jun
TI  - Generation and expression analysis of BAC humanized mice carrying HLA-DP401 
      haplotype.
PG  - 116-128
LID - 10.1002/ame2.12158 [doi]
AB  - BACKGROUND: Human leukocyte antigen (HLA)-DP is much less studied than other HLA 
      class II antigens, that is, HLA-DR and HLA-DQ, etc. However, the accumulating 
      data have suggested the important roles of DP-restricted responses in the context 
      of cancer, allergy, and infectious disease. Lack of animal models expressing 
      these genes as authentic cis-haplotypes blocks our understanding for the role of 
      HLA-DP haplotypes in immunity. METHODS: To explore the potential cis-acting 
      control elements involved in the transcriptional regulation of the HLA-DPA1/DPB1 
      gene, we performed the expression analysis using bacterial artificial chromosome 
      (BAC)-based transgenic humanized mice in the C57BL/6 background, which carried 
      the entire HLA-DP401 gene locus. We further developed a mouse model of 
      Staphylococcus aureus pneumonia in HLA-DP401 humanized transgenic mice, and 
      performed the analysis on the expression pattern of HLA-DP401 and immunological 
      responses in the model. RESULTS: In this study, we screened and identified a BAC 
      clone spanning the entire HLA-DP gene locus. DNA from this clone was analyzed for 
      integrity by pulsed-field gel electrophoresis and then microinjected into 
      fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR 
      primers for regional markers with an average distance of 15 kb between each 
      primer were used to confirm the integrity of the transgene in the five transgenic 
      lines carrying the HLA-DPA1/DPB1 gene. Transgene copy numbers were determined by 
      real-time PCR analysis. HLA-DP401 gene expression was analyzed at the mRNA and 
      protein level. Although infection with S aureus Newman did not alter the 
      percentage of immune cells in the spleen and thymus from the HLA-DP401-H2-Abeta1 
      humanized mice. Increased expression of HLA-DP401 was observed in the thymus of 
      the humanized mice infected by S aureus. CONCLUSIONS: We generated several BAC 
      transgenic mice, and analyzed the expression of HLA-DPA1/DPB1 in those mice. A 
      model of Saureus-induced pneumonia in the HLA-DP401-H2-Abeta1(-/-) humanized mice 
      was further developed, and S aureus infection upregulated the HLA-DP401 
      expression in thymus of those humanized mice. These findings demonstrate the 
      potential of those HLA-DPA1/DPB1 transgenic humanized mice for developing animal 
      models of infectious diseases and MHC-associated immunological diseases.
CI  - (c) 2021 The Authors. Animal Models and Experimental Medicine published by John 
      Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory 
      Animal Sciences.
FAU - Li, Feng
AU  - Li F
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Zhu, Meng-Min
AU  - Zhu MM
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Niu, Bo-Wen
AU  - Niu BW
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Liu, Ling-Ling
AU  - Liu LL
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Peng, Xiu-Hua
AU  - Peng XH
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Yang, Hua
AU  - Yang H
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Qin, Bo-Yin
AU  - Qin BY
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Wang, Meixiang
AU  - Wang M
AD  - Department of Scientific Research Shanghai Public Health Clinical Center Fudan 
      Univeristy Shanghai China.
FAU - Ren, Xiaonan
AU  - Ren X
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
FAU - Zhou, Xiaohui
AU  - Zhou X
AD  - Department of Laboratory Animal Science Shanghai Public Health Clinical Center 
      Fudan Univeristy Shanghai China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210323
PL  - United States
TA  - Animal Model Exp Med
JT  - Animal models and experimental medicine
JID - 101726292
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DQ Antigens)
SB  - IM
MH  - Animals
MH  - Chromosomes, Artificial, Bacterial/genetics
MH  - *HLA-DP Antigens/genetics
MH  - *HLA-DQ Antigens/genetics
MH  - Haplotypes
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC8212823
OTO - NOTNLM
OT  - HLA-DP4
OT  - Staphylococcus aureus pneumonia
OT  - bacterial artificial chromosome (BAC)
OT  - gene expression
OT  - humanized mice
EDAT- 2021/06/29 06:00
MHDA- 2021/10/26 06:00
PMCR- 2021/03/23
CRDT- 2021/06/28 06:12
PHST- 2020/07/10 00:00 [received]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2021/06/28 06:12 [entrez]
PHST- 2021/06/29 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/03/23 00:00 [pmc-release]
AID - AME212158 [pii]
AID - 10.1002/ame2.12158 [doi]
PST - epublish
SO  - Animal Model Exp Med. 2021 Mar 23;4(2):116-128. doi: 10.1002/ame2.12158. 
      eCollection 2021 Jun.