title: Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage.
abstract: Presenilin-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.
authors: Department of Pharmaceutical Pharmacology, School of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama 790-8578, Ehime, Japan. mnakajim@cc.matsuyama-u.ac.jp
authors: Mitsunari
authors: M
authors: Nakajima
authors: Sono
authors: S
authors: Watanabe
authors: Satoshi
authors: S
authors: Okuyama
authors: Jie
authors: J
authors: Shen
authors: Yoshiko
authors: Y
authors: Furukawa
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053764:Presenilin-1; D007334:Insulin-Like Growth Factor I