| First Author | Lindfors PH | Year | 2006 |
| Journal | Endocrinology | Volume | 147 |
| Issue | 5 | Pages | 2237-44 |
| PubMed ID | 16497798 | Mgi Jnum | J:108404 |
| Mgi Id | MGI:3623870 | Doi | 10.1210/en.2005-1620 |
| Citation | Lindfors PH, et al. (2006) Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor alpha4 impairs thyroid calcitonin production in young mice. Endocrinology 147(5):2237-44 |
| abstractText | Glial cell line-derived neurotrophic factor family receptor (GFRalpha) 4, the binding receptor for persephin, is coexpressed with the signaling Ret receptor tyrosine kinase predominantly in thyroid calcitonin-producing C cells. We show by in situ hybridization and immunohistochemistry that the functional, glycolipid-anchored form of GFRalpha4 is produced in mouse only in the C cells but not in parathyroid gland or in the brain. C cells expressed functional GFRalpha4 throughout postnatal development, whereas Ret expression in these cells decreased postnatally and was undetectable in adults. To understand the physiological role of GFRalpha4, we produced GFRalpha4-deficient [knockout (KO)] mice. No differences were observed between wild-type and GFRalpha4-KO littermate animals in growth, gross behavior, or viability. The number and morphology of the thyroid C cells were indistinguishable between the genotypes in both newborn and adult age. However, thyroid tissue calcitonin content was reduced by 60% in newborn and by 45% in 3-wk-old GFRalpha4-KO mice compared with wild-type controls. In contrast, thyroid calcitonin levels were similar in adult animals. Consistent with the reduced calcitonin levels, bone formation rate in juvenile GFRalpha4-KO mice was increased. In conclusion, this study indicates a novel role for endogenous GFRalpha4 signaling in regulating calcitonin production in thyroid C cells of young mice. |
