STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone

Thilini H. Gamage; Emma Lengle; Gjermund Gunnes; Helen Pullisaar; Asbjørn Holmgren; Janne E. Reseland; Else Merckoll; Stefania Corti; Masahiro Mizobuchi; Raul J. Morales; Leonidas Tsiokas; Geir E. Tjønnfjord; Rodrigo S. Lacruz; Staale P. Lyngstadaas; Doriana Misceo; Eirik Frengen

doi:10.1016/j.ceca.2019.102110

STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone

Thilini H. Gamage, Emma Lengle, Gjermund Gunnes, Helen Pullisaar, Asbjørn Holmgren, Janne E. Reseland, Else Merckoll, Stefania Corti, Masahiro Mizobuchi, Raul J. Morales, Leonidas Tsiokas, Geir E. Tjønnfjord, Rodrigo S. Lacruz, Staale P. Lyngstadaas, Doriana Misceo, Eirik Frengen

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1^R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1^R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1^R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1^R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1^R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1^R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate.

Original language	English (US)
Article number	102110
Journal	Cell Calcium
Volume	85
DOIs	https://doi.org/10.1016/j.ceca.2019.102110
State	Published - Jan 2020

Keywords

Abnormal bone architecture
Ectopic hair growth
STIM1 R304W
Skeletal defects
Stormorken syndrome

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

Access to Document

10.1016/j.ceca.2019.102110

Cite this

Gamage, T. H., Lengle, E., Gunnes, G., Pullisaar, H., Holmgren, A., Reseland, J. E., Merckoll, E., Corti, S., Mizobuchi, M., Morales, R. J., Tsiokas, L., Tjønnfjord, G. E., Lacruz, R. S., Lyngstadaas, S. P., Misceo, D., & Frengen, E. (2020). STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone. Cell Calcium, 85, Article 102110. https://doi.org/10.1016/j.ceca.2019.102110

Gamage, TH, Lengle, E, Gunnes, G, Pullisaar, H, Holmgren, A, Reseland, JE, Merckoll, E, Corti, S, Mizobuchi, M, Morales, RJ, Tsiokas, L, Tjønnfjord, GE, Lacruz, RS, Lyngstadaas, SP, Misceo, D & Frengen, E 2020, 'STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone', Cell Calcium, vol. 85, 102110. https://doi.org/10.1016/j.ceca.2019.102110

@article{7ada8a1ee9e6449b9fc617ae9bb49971,

title = "STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone",

abstract = "Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate.",

keywords = "Abnormal bone architecture, Ectopic hair growth, STIM1 R304W, Skeletal defects, Stormorken syndrome",

author = "Gamage, {Thilini H.} and Emma Lengle and Gjermund Gunnes and Helen Pullisaar and Asbj{\o}rn Holmgren and Reseland, {Janne E.} and Else Merckoll and Stefania Corti and Masahiro Mizobuchi and Morales, {Raul J.} and Leonidas Tsiokas and Tj{\o}nnfjord, {Geir E.} and Lacruz, {Rodrigo S.} and Lyngstadaas, {Staale P.} and Doriana Misceo and Eirik Frengen",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2020",

month = jan,

doi = "10.1016/j.ceca.2019.102110",

language = "English (US)",

volume = "85",

journal = "Cell Calcium",

issn = "0143-4160",

publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone

AU - Gamage, Thilini H.

AU - Lengle, Emma

AU - Gunnes, Gjermund

AU - Pullisaar, Helen

AU - Holmgren, Asbjørn

AU - Reseland, Janne E.

AU - Merckoll, Else

AU - Corti, Stefania

AU - Mizobuchi, Masahiro

AU - Morales, Raul J.

AU - Tsiokas, Leonidas

AU - Tjønnfjord, Geir E.

AU - Lacruz, Rodrigo S.

AU - Lyngstadaas, Staale P.

AU - Misceo, Doriana

AU - Frengen, Eirik

PY - 2020/1

Y1 - 2020/1

N2 - Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate.

AB - Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate.

KW - Abnormal bone architecture

KW - Ectopic hair growth

KW - STIM1 R304W

KW - Skeletal defects

KW - Stormorken syndrome

UR - http://www.scopus.com/inward/record.url?scp=85075534076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075534076&partnerID=8YFLogxK

U2 - 10.1016/j.ceca.2019.102110

DO - 10.1016/j.ceca.2019.102110

M3 - Article

C2 - 31785581

AN - SCOPUS:85075534076

SN - 0143-4160

VL - 85

JO - Cell Calcium

JF - Cell Calcium

M1 - 102110

ER -

STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this