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The Shisa3 knockout mouse exhibits normal bone phenotype.

Kohei Murakami1, He Zhifeng2, Takako Suzuki3

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SHISA3, a Wnt inhibitor, is expressed in mouse bone but does not significantly impact bone development in knockout models. This suggests functional redundancy with other Shisa family members in skeletal biology.

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Area of Science:

  • Bone biology
  • Skeletal development
  • Cell signaling

Background:

  • Wnt signaling is crucial for skeletal development and bone metabolism.
  • Wnt inhibitory factors regulate bone metabolism.
  • SHISA3 inhibits Wnt/β-catenin signaling in lung cancer but its role in bone is unknown.

Purpose of the Study:

  • To investigate the function of SHISA3 in mouse bone biology and skeletal development.

Main Methods:

  • Assessed SHISA3 expression in mouse calvarial bones.
  • Utilized adenovirus-mediated gene transfer to inhibit Wnt signaling.
  • Performed phenotypic analysis of Shisa3 knockout mice using micro-computed tomography and gene expression analysis.
  • Examined Wnt target gene expression in calvariae of Shisa3 knockout and wild-type mice.
  • Analyzed Axin2-expressing cells in Axin2Cre/ERT2 knock-in mice.

Main Results:

  • SHISA3 is highly expressed in osteoblasts within mouse calvarial bones.
  • Adenovirus-mediated SHISA3 expression inhibited Wnt3a-induced β-catenin nuclear translocation and Axin2 expression.
  • Shisa3 knockout mice showed no significant differences in bone phenotype, osteoblast marker expression, or skeletal development compared to wild-type mice.
  • No significant differences in canonical Wnt signaling target gene expression were observed in Shisa3 knockout mice.
  • The number of Axin2-expressing cells was comparable between Shisa3 knockout and control mice.

Conclusions:

  • SHISA3 is expressed in bone cells but does not appear to play a critical role in skeletal development.
  • Functional redundancy among Shisa family members likely accounts for the lack of a phenotype in Shisa3 knockout mice.
  • Further research is needed to elucidate the specific roles of other Shisa family members in bone metabolism.