title: Gene expression profiling of allogeneic islet grafts in an experimental mouse model before rejection or tolerance phenotypes arise.
abstract: BACKGROUND
  It has been reported that an HY antigen-mismatched islet transplantation can induce peripheral tolerance. However, the factors that initiate the peripheral tolerance are not clear. This study was designed to examine which genes were most important for the induction of peripheral tolerance.
  
  
  METHODS
  Islets from female Balb/c and male C57BL/6 mice were transplanted underneath the left perirenal capsule of female C57BL/6 recipient mice rendered diabetic by intraperitoneal injection of streptozotocin. Before rejection or tolerance phenotypes arose, we harvested islet grafts for cDNA microarray analysis.
  
  
  RESULTS
  Minor antigen-mismatched islets transplanted into recipient mice showed no rejection or tolerance phenotypes until 12 days posttransplantation. When we confirmed, decreased functional islet grafts and increased inflammatory cell infiltration. Gene expression profiles revealed differences in expression among groups. Major histocompatibility complex-mismatched islets induced upregulation of 209 genes and downregulation of 10 genes compared with the HY antigen-mismatched islet (2-fold; P < .05). Of these, 3 genes exhibited significant changes in expression levels in Balb/c donor islet grafts compared with C57BL/6 donor islet grafts: Gad1, Gdf10, and Scg2 (P < .01).
  
  
  CONCLUSIONS
  The present study suggested that 3 genes showed a significant relationship to protection against graft rejection. The identification of these genes may help to understand signaling pathways, involved in the communication between transplanted islet grafts and recipients in vivo.
authors.affiliation: Integrative Bioscience and Biotechnology, POSTECH, Hyojadong, Nam-Gu, Pohang, Republic of Korea.
authors.forename: S-E
authors.initials: SE
authors.lastname: Choi
authors.forename: J-R
authors.initials: JR
authors.lastname: Noh
authors.forename: J
authors.initials: J
authors.lastname: Seo
authors.forename: K-J
authors.initials: KJ
authors.lastname: Yang
authors.forename: M-C
authors.initials: MC
authors.lastname: Kook
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002262:Carboxy-Lyases / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000601:surgery*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000235:genetics*; D055413:Growth Differentiation Factor 10 / Q000235:genetics; D006182:H-Y Antigen / Q000276:immunology; D006648:Histocompatibility / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D053381:Secretogranin II / Q000235:genetics; D013997:Time Factors; D046509:Tissue Culture Techniques; D023001:Transplantation Tolerance / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C525784:Gdf10 protein, mouse; D055413:Growth Differentiation Factor 10; D006182:H-Y Antigen; D007328:Insulin; D053381:Secretogranin II; C506138:secretogranin 2, mouse; D002262:Carboxy-Lyases; C578088:GADL1 protein, mouse