The Shisa3 knockout mouse exhibits normal bone phenotype

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 Axin2^Cre/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.