2000 Fiscal Year Final Research Report Summary
Title of progect : Identification of the responsible gene in a novel murine model with atopic dermatitis
| Project/Area Number |
11670769
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kumamoto University |
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Principal Investigator |
ADACHI Naoto Kumamoto University School of Medicine Department of Hospital Lecturer, 医学部・附属病院, 講師 (00264292)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Hideki Hamamatsu Medical School Experimental Animal Institute Assistant Professor, 助教授 (30142053)
MATSUURA Toshinobu Ryukyu University School of Medicine Department of Pediatrics Assistant Professor, 医学部, 助教授 (00315467)
橋山 元浩 熊本大学, 医学部・附属病院, 医員
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| Project Period (FY) |
1999 – 2000
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| Keywords | atopic dermatitis / murine model / Th1 / Th2 ratio / responsible gene locus |
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| Research Abstract |
Autosomal recessive mutation arose spontaneously on the ICR starin background. The mouse is identified by the large flakes of cornified debris with alopecia and small constitute compared with their normal littermates. Microscopic examinations show epidermal hyperplasia, diffuse orthokeratosis and massive infiltration of lymphocytes in subcutaneous tissue. Lymphoid organs show a remarkable changes ; Thymic histology showe a markedly reduced cortex cellularity and spleen weight was significantly increased with disturbed architacture. Furthermore massive infiltration of lymphocyte is found in liver and lung. These pathological changes are found in 2-week-old mutant, suggesting that the mouse has inborn errors of lymphoid tissue development. Flowcytometric analysis show a reduction in CD3, CD4 and CD8 fraction and increase of B220 and Mac-1 fraction in spleen cells and cytokine prodction profile deviated to Th2 pattern compared with normal littermates.
To map the responsible gene, int, the mouse is backcrossed to MSM strain.
Recombination frequences, a ratio of int^<-/-> to int^<-/+>, are analysed with microsatellite markers in (int^<-/+> X MSM^<+/+>) F1 X int^<-/+> F2 offspring. The int locus is assigned to chromosome 17 and int gene is most closely linked to SSLP marker D17Mit41 (51.9cM) and D17Mit122(53cM). This result places int locus near the distal end of chromosome 17.
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