Disruption of the c‐terminal serine protease domain of Fam111a does not alter calcium homeostasis in mice

Rebecca Siu Ga Tan; Christy Hui Lin Lee; Wanling Pan; Serene Wohlgemuth; Michael R. Doschak; R. Todd Alexander

doi:10.14814/phy2.15977

journal article Open Access May 01, 2024

Disruption of the c‐terminal serine protease domain of Fam111a does not alter calcium homeostasis in mice

Rebecca Siu Ga Tan

Christy Hui Lin Lee Wanling Pan Serene Wohlgemuth Michael R. Doschak R. Todd Alexander

Physiological Reports Vol. 12 No. 9 · Wiley

View at Publisher Save 10.14814/phy2.15977

Abstract

AbstractFAM111A gene mutations cause Kenney–Caffey syndrome (KCS) and Osteocraniostenosis (OCS), conditions characterized by short stature, low serum ionized calcium (Ca2+), low parathyroid hormone (PTH), and bony abnormalities. The molecular mechanism mediating this phenotype is unknown. The c‐terminal domain of FAM111A harbors all the known disease‐causing variations and encodes a domain with high homology to serine proteases. However, whether this serine protease domain contributes to the maintenance of Ca2+ homeostasis is not known. We hypothesized the disruption of the serine protease domain of FAM111A would disrupt Ca2+ homeostasis. To test this hypothesis, we generated with CRISPR/Cas9, mice with a frameshift insertion (c.1450insA) or large deletion (c.1253‐1464del) mutation in the Fam111a serine protease domain. Serum‐ionized Ca2+ and PTH levels were not significantly different between wild type, heterozygous, or homozygous Fam111a mutant mice. Additionally, there were no significant differences in fecal or urine Ca2+ excretion, intestinal Ca2+ absorption or overall Ca2+ balance. Only female homozygous (c.1450insA), but not heterozygous mice displayed differences in bone microarchitecture and mineral density compared to wild‐type animals. We conclude that frameshift mutations that disrupt the c‐terminal serine protease domain do not induce a KCS or OCS phenotype in mice nor alter Ca2+ homeostasis.

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References

Details

Published: May 01, 2024
Vol/Issue: 12(9)
License: View

Authors

R

Rebecca Siu Ga Tan

Department of Physiology University of Alberta Edmonton Alberta Canada; Membrane Protein Disease Research Group University of Alberta Edmonton Alberta Canada; The Women and Children's Health Research Institute Edmonton Alberta Canada

C

Christy Hui Lin Lee

Department of Physiology University of Alberta Edmonton Alberta Canada; Membrane Protein Disease Research Group University of Alberta Edmonton Alberta Canada; The Women and Children's Health Research Institute Edmonton Alberta Canada

W

Wanling Pan

Department of Physiology University of Alberta Edmonton Alberta Canada; Membrane Protein Disease Research Group University of Alberta Edmonton Alberta Canada

S

Serene Wohlgemuth

Department of Medicine University of Alberta Edmonton Alberta Canada

M

Michael R. Doschak

Faculty of Pharmacy & Pharmaceutical Sciences University of Alberta Edmonton Alberta Canada

R

R. Todd Alexander

Department of Physiology University of Alberta Edmonton Alberta Canada; Membrane Protein Disease Research Group University of Alberta Edmonton Alberta Canada; The Women and Children's Health Research Institute Edmonton Alberta Canada; Department of Pediatrics University of Alberta Edmonton Alberta Canada

Funding

Canadian Institutes of Health Research Award: 166072

Cite This Article

Rebecca Siu Ga Tan, Christy Hui Lin Lee, Wanling Pan, et al. (2024). Disruption of the c‐terminal serine protease domain of Fam111a does not alter calcium homeostasis in mice. Physiological Reports, 12(9). https://doi.org/10.14814/phy2.15977

Disruption of the c‐terminal serine protease domain of Fam111a does not alter calcium homeostasis in mice

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