| Budget Amount *help |
¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Presenilin 1 (PS1) is a gene responsible for the development of early-onset familial Alzheimer's disease. In a previous study, the head investigator generated a Wntl-cre-induced presenilin-1-cKO mice, in which the expression of PS1 is abrogated in the cells derived from neural crest. The hypertrophy of the skull vault and the reduced growth of the trunk region were the prominent features of the conditional knockout mice. In the present study, I tried to investigate the mechanisms of skull vault formation and of the growth control using the mutant mice.
In 2006, I examined the morphology of the cranial skeleton of new born mice and found that the embryonic development of the mice is normal. Also, no abnormalities were detected in the migration of the cells from the neural crest. These results suggested that the malformation of the skull vault is not the primary event in the phenotypes of the mutant.
In 2007, I investigated the endocrine system of the mutant mice because I suspected that an abnormality in hormonal regulations might affect the development of skull vault and the growth of the trunk region after birth. I first tried to detect the growth hormone (GH) in the serum because the reduction of the body weight was prominent after 3-weeks old. Although I failed to detect GH in the mutant sera as well as the control ones, I found the obvious difference in the levels of IGF-I in the sera which are known to be regulated by GH levels. The levels of IGF-I was clearly reduced in the sera of the mutant mice. The pathological analysis revealed the atrophy in the anterior lobe of the pituitary. These results suggest that PS1 in the lineage of neural crest cells controls the development of the anterior lobe of the pituitary although further analysis is required. In the future study, I will perform the immunohistochemical analysis and the quantitative RT-PCR analysis for pituitary hormones such as GH, TSH, ACTH, FSH, LH, and PRL.
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