2003 Fiscal Year Final Research Report Summary
Molecular Pathological Aspects of Spontaneous Mouse Hereditary Keratoconus
| Project/Area Number |
12470370
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | NIIGATA UNIVERSITY (2003)
Research Institute for Clinical Oncology, Saitama Cancer Center (2000-2002) |
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Principal Investigator |
TACHIBANA Masayoshi NIIGATA UNIVERSITY, Brain Research Institute, Professor, 脳研究所, 教授 (10128712)
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Wakako Kyoto Prefectural University of Medicine, Ophthalmology, Assistant, 眼科学教室, 助手 (90326231)
KINOSHITA Shigeru Kyoto Prefectural University of Medicine, Ophthalmology, Professor, 眼科学教室, 教授 (30116024)
MATSUSHIMA Yoshibumi Saitma Cancer Center, Specialized Research, Investigator, 研究室・主任研究員 (10094955)
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| Project Period (FY) |
2000 – 2003
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| Keywords | mouse / spontaneous / hereditary / keratoconus / androgen-dependent / SKC / JKC |
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| Research Abstract |
Two lines of mouse with spontaneous hereditary keratoconus-like keratopathy were discovered in Saitama Cancer Center, which were named SKC (spontaneous keratoconus) and JKC (Japanese Keratoconus) mouse. SKC mouse was found in a closed colony of laboratory mouse, while JKC mouse was found in Japanese wild mice (Mus musculus molossinus). In this study, we characterized these mice and their corneas with special interests in their molecular-pathological and genetic aspects. Keratopathy of both SKC and JKC mice was inherited in an autosomal recessive manner, and linkage analyses in SKC mouse and JKC mouse linked each responsible or susceptible gene, to respectively, mouse chromosome 17 and 13.
While keratopathy of JKC mice occurred in both genders that of SKC mice occurred selectively in males (keratopathy occurred only in extremely rare cases in female SKC mice). Interestingly, however, in female SKC mice the keratopathy appeared in many cases (66%) when androgen was given to them at approximately 4 weeks of age. These suggest that keratopathy of SKC mice is androgen-dependent (requires androgen to occur). In an effort to reveal the mechanism of this androgen-dependency, we examined the expression of androgen in mouse corneas. Expression of androgen receptors was detected in nuclei of various types of corneal cells as judged by immunohistochemistry, and expression of this receptor at RNA level was also detected by RT-PCR in mouse corneas. These suggest that androgen directly acts in corneal cells to cause keratopathy. In addition, we found that not only androgen receptor but also estrogen receptors of both a and b type are expressed in mouse corneas. further study revealed that sex steroid receptors are expressed in human corneas as well. Sex steroids may play an important role in development of keratoconus and other keratopthy in SKC mice and perhaps other mice or even in humans.
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