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Loss of Memo, a novel FGFR regulator, results in reduced lifespan
Author(s) -
Haenzi Barbara,
Bonny Olivier,
Masson Régis,
Lienhard Susanne,
Dey Julien H.,
Kuroo Makoto,
Hynes Nancy E.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-228320
Subject(s) - knockout mouse , fibroblast growth factor receptor , fibroblast growth factor , conditional gene knockout , microbiology and biotechnology , endocrinology , medicine , regulator , fibroblast growth factor 23 , biology , calcium , receptor , phenotype , genetics , gene , parathyroid hormone
Memo is a widely expressed 33‐kDa protein required for heregulin (HRG)‐, epidermal growth factor (EGF)‐, and fibroblast growth factor (FGF)‐induced cell motility. Studies in mouse embryonic fibroblasts, wild‐type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional‐knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo‐knockout mice also have elevated serum levels of active vitamin D, 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH) 2 D production and normal calcium homeostasis.—Haenzi, B., Bonny, O., Masson, R., Lienhard, S., Dey, J. H., Kuro‐o, M., Hynes, N. E. Loss of Memo, a novel FGFR regulator, results in reduced lifespan. FASEB J. 28, 327–336 (2014). www.fasebj.org