Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor 4 impairs thyroid calcitonin production in young mice

Päivi H Lindfors, Maria Lindahl, Jari Rossi, Mart Saarma, Matti S Airaksinen, Matti Sakari Airaksinen

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Glial cell line-derived neurotrophic factor family receptor (GFR alpha) 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 GFR alpha 4 is produced in mouse only in the C cells but not in parathyroid gland or in the brain. C cells expressed functional GFR alpha 4 throughout postnatal development, whereas Ret expression in these cells decreased postnatally and was undetectable in adults. To understand the physiological role of GFR alpha 4, we produced GFR alpha 4-deficient [knockout (KO)] mice. No differences were observed between wild-type and GFR alpha 4-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 GFR alpha 4-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 GFR alpha 4-KO mice was increased. In conclusion, this study indicates a novel role for endogenous GFR alpha 4 signaling in regulating calcitonin production in thyroid C cells of young mice.
    Original languageEnglish
    JournalEndocrinology
    Volume147
    Issue number5
    Pages (from-to)2237-2244
    Number of pages8
    ISSN0013-7227
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine
    • 118 Biological sciences
    • 515 Psychology

    Cite this

    @article{1bfea5c89be4498181d63c491fcfbc21,
    title = "Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor 4 impairs thyroid calcitonin production in young mice",
    abstract = "Glial cell line-derived neurotrophic factor family receptor (GFR alpha) 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 GFR alpha 4 is produced in mouse only in the C cells but not in parathyroid gland or in the brain. C cells expressed functional GFR alpha 4 throughout postnatal development, whereas Ret expression in these cells decreased postnatally and was undetectable in adults. To understand the physiological role of GFR alpha 4, we produced GFR alpha 4-deficient [knockout (KO)] mice. No differences were observed between wild-type and GFR alpha 4-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 GFR alpha 4-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 GFR alpha 4-KO mice was increased. In conclusion, this study indicates a novel role for endogenous GFR alpha 4 signaling in regulating calcitonin production in thyroid C cells of young mice.",
    keywords = "311 Basic medicine, 118 Biological sciences, 515 Psychology",
    author = "Lindfors, {P{\"a}ivi H} and Maria Lindahl and Jari Rossi and Mart Saarma and Airaksinen, {Matti S} and Airaksinen, {Matti Sakari}",
    year = "2006",
    doi = "10.1210/en.2005-1620",
    language = "English",
    volume = "147",
    pages = "2237--2244",
    journal = "Endocrinology",
    issn = "0013-7227",
    publisher = "Endocrine Society",
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    }

    Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor 4 impairs thyroid calcitonin production in young mice. / Lindfors, Päivi H; Lindahl, Maria; Rossi, Jari; Saarma, Mart; Airaksinen, Matti S; Airaksinen, Matti Sakari.

    In: Endocrinology, Vol. 147, No. 5, 2006, p. 2237-2244.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor 4 impairs thyroid calcitonin production in young mice

    AU - Lindfors, Päivi H

    AU - Lindahl, Maria

    AU - Rossi, Jari

    AU - Saarma, Mart

    AU - Airaksinen, Matti S

    AU - Airaksinen, Matti Sakari

    PY - 2006

    Y1 - 2006

    N2 - Glial cell line-derived neurotrophic factor family receptor (GFR alpha) 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 GFR alpha 4 is produced in mouse only in the C cells but not in parathyroid gland or in the brain. C cells expressed functional GFR alpha 4 throughout postnatal development, whereas Ret expression in these cells decreased postnatally and was undetectable in adults. To understand the physiological role of GFR alpha 4, we produced GFR alpha 4-deficient [knockout (KO)] mice. No differences were observed between wild-type and GFR alpha 4-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 GFR alpha 4-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 GFR alpha 4-KO mice was increased. In conclusion, this study indicates a novel role for endogenous GFR alpha 4 signaling in regulating calcitonin production in thyroid C cells of young mice.

    AB - Glial cell line-derived neurotrophic factor family receptor (GFR alpha) 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 GFR alpha 4 is produced in mouse only in the C cells but not in parathyroid gland or in the brain. C cells expressed functional GFR alpha 4 throughout postnatal development, whereas Ret expression in these cells decreased postnatally and was undetectable in adults. To understand the physiological role of GFR alpha 4, we produced GFR alpha 4-deficient [knockout (KO)] mice. No differences were observed between wild-type and GFR alpha 4-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 GFR alpha 4-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 GFR alpha 4-KO mice was increased. In conclusion, this study indicates a novel role for endogenous GFR alpha 4 signaling in regulating calcitonin production in thyroid C cells of young mice.

    KW - 311 Basic medicine

    KW - 118 Biological sciences

    KW - 515 Psychology

    U2 - 10.1210/en.2005-1620

    DO - 10.1210/en.2005-1620

    M3 - Article

    VL - 147

    SP - 2237

    EP - 2244

    JO - Endocrinology

    JF - Endocrinology

    SN - 0013-7227

    IS - 5

    ER -