| Project/Area Number |
09670893
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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 |
Dermatology
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
YAMANISHI Kiyofumi KYOTO PREFECTURAL UNIVERSITY OF MEDICINE,DEPARTMENT,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (10182586)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | GENE TARGETING / TRANSGENIC MICE / TRANSGLUTAMINASE / GENE THERAPY / トランスグルタミナーゼ1 |
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| Research Abstract |
We generated transgenic mice expressing the Escherichia coli beta-galactosidase gene (lalphaZ) directed by the 5' upstream region of human transglutaminase 1 (TGase 1) gene. beta-Galactosidase histochemistry revealed that the TGMI-lalphaZ transgene was expressed in terminally differentiating keratinocytes of the upper layers of the stratified squamous epithelia in embryonic, neonatal and adult transgenic mice. The expression pattern was similar to that of endogenous TGase 1 niRNA detected by in situ hybridization. Furthermore, topical application of a phorbol ester on the adult tail skin enhanced expression of the transgene as well as TGase 1 mRNA in the epidermis. Thus, the 2.5-kb 5' upstream sequence of the human TGase 1 gene may be useful for epidermis and terminal differentiation-specific gene therapy in the stratified squamous epithelia.
Next, we generated mice lacking the TGase 1 gene, and showed that they have erythrodermic skin with abnormal keratinization. In their stratum corneum, degradation of nuclei and keratohy aim F-granules was incomplete and cell envelope assembly was defective. The skin barrier function of TGase 1-null mice was markedly impaired, and these mice died within 4-5 h after birth. These results clearly demonstrate that the TGase 1 gene is essential to the development and maturation of the stratum corneum and to adaptation to the environment after birth. Thus, these TGase 1 knock-out mice may be a useful model for severe cases of LI gene therapy.
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