Restricted growth and insulin‐like growth factor‐1 deficiency in mice lacking presenilin‐1 in the neural crest cell lineage

International Journal of Developmental Neuroscience - Tập 27 - Trang 837-843 - 2009
Mitsunari Nakajima1, Sono Watanabe1, Satoshi Okuyama1, Jie Shen2, Yoshiko Furukawa1
1Department of Pharmaceutical Pharmacology, School of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama 790-8578, Ehime, Japan
2Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA

Tóm tắt

AbstractPresenilin‐1 (PS1) is a transmembrane protein that is in many cases responsible for the development of early‐onset familial Alzheimer's disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis, and cardiac morphogenesis. We report here that PS1 is also required for maturation and/or maintenance of the pituitary gland. We generated PS1‐conditional knockout (PS1‐cKO) mice by crossing floxed PS1 and Wnt1‐cre mice, in which PS1 was lacking in the neural crest‐derived cell lineage. Although the PS1‐cKO mice exhibited no obvious phenotypic abnormalities for several days after birth, reduced body weight in the mutant was evident by the age of 3–5 weeks. Pituitary weight and serum insulin‐like growth factor (IGF)‐1 level were also reduced in the mutant. Histologic analysis revealed severe atrophy of the cytosol in the anterior and intermediate pituitary lobes of the mutant. Immunohistochemistry did not reveal clear differences in the expression levels of thyroid‐stimulating hormone, adrenocorticotropic hormone, or prolactin in the mutant pituitary. In contrast, growth hormone expression levels were reduced in the anterior lobe of the mutant. PS1 was defective in the posterior lobe, but not the anterior or intermediate lobes, in the mutant pituitary. These findings suggest that PS1 indirectly mediates the development and/or maintenance of the anterior and intermediate lobes in the pituitary gland via actions in other regions, such as the posterior lobe.

Tài liệu tham khảo

10.1016/S0092-8674(05)80085-6 10.1016/j.ydbio.2003.10.039 10.1242/dev.128.24.5189 10.1242/dev.127.8.1671 Couly G., 1988, The fate map of the cephalic neural primordium at the presomitic to the 3‐somite stage in the avian embryo, Development, 103, 101, 10.1242/dev.103.Supplement.101 10.1074/jbc.M500621200 10.3109/07853899809002605 10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J 10.1016/S0960-9822(07)00562-3 10.1111/j.1365-2265.2005.02289.x 10.1210/edrv-10-1-68 10.1038/19083 10.1677/joe.0.1360091 10.1101/gad.13.21.2801 10.1002/neu.480210305 10.1083/jcb.200402153 10.1242/dev.127.12.2593 10.1242/dev.127.8.1607 10.1016/S0092-8674(02)00970-4 10.1016/0092-8674(91)90574-I 10.1242/dev.128.8.1391 10.1038/nm1065 10.1073/pnas.96.9.5037 10.1093/emboj/21.8.1948 10.1016/j.cell.2003.08.008 10.1210/en.2002-220948 10.1002/dvdy.20098 10.1016/S0925-4773(03)00064-9 10.1016/S0896-6273(04)00182-5 10.1016/S0092-8674(00)80244-5 10.1093/emboj/19.20.5460 10.1101/gad.12.11.1691 10.1038/387288a0 10.1016/S0896-6273(01)00417-2 10.1002/jnr.10430 10.1101/gad.1444706
Thông tin
Thông tin xuất bản

International Journal of Developmental Neuroscience

Tập 27

837-843

Thông tin tác giả