Related Experiment Video
Updated: Jun 8, 2026
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice
Nobutaka Hanagata1, Xianglan Li, Hiromi Morita
1Nanotechnology Innovation Center, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan. HANAGATA.Nobutaka@nims.go.jp
Abstract:
Interferon-inducible transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein whose expression peaks around the early mineralization stage during the osteoblast maturation process. To investigate IFITM5 function, we first sought to identify which proteins interact with IFITM5. Liquid chromatography mass spectrometry revealed that FK506-binding protein 11 (FKBP11) co-immunoprecipitated with IFITM5. FKBP11 is the only protein it was found to interact with in osteoblasts, while IFITM5 interacts with several proteins in fibroblasts. FKBPs are involved in protein folding and immunosuppressant binding, but we could not be sure that IFITM5 participated in these activities when bound to FKBP11. Thus, we generated Ifitm5-deficient mice and analyzed their skeletal phenotypes. The skeletons, especially the long bones, of homozygous mutants (Ifitm5(-/-)) were smaller than those of heterozygous mutants (Ifitm5(+/-)), although we did not observe any significant differences in bone morphometric parameters. The effect of Ifitm5 deficiency on bone formation was more significant in newborns than in young and adult mice, suggesting that Ifitm5 deficiency might have a greater effect on prenatal bone development. Overall, the effect of Ifitm5 deficiency on bone formation was less than we expected. We hypothesize that this may have resulted from a compensatory mechanism in Ifitm5-deficient mice.
Insights
Interferon-inducible transmembrane protein 5 (IFITM5) is crucial for bone development. While IFITM5 deficiency in mice resulted in smaller skeletons, especially in newborns, compensatory mechanisms may explain the limited overall impact on bone formation.
Area of Science:
- Biochemistry
- Molecular Biology
- Skeletal Biology
Background:
- Interferon-inducible transmembrane protein 5 (IFITM5) is an osteoblast-specific protein.
- Its expression peaks during early osteoblast mineralization.
- Understanding IFITM5's function and interactions is key to skeletal development research.
Purpose of the Study:
- To identify proteins interacting with IFITM5 in osteoblasts.
- To investigate the role of IFITM5 in skeletal development using a mouse model.
Main Methods:
- Co-immunoprecipitation and liquid chromatography-mass spectrometry to identify interacting proteins.
- Generation and phenotypic analysis of Ifitm5-deficient mice (Ifitm5(-/-)).
- Skeletal and bone morphometric analysis of mutant and wild-type mice.
Main Results:
- FK506-binding protein 11 (FKBP11) was identified as an IFITM5-interacting protein in osteoblasts.
- Ifitm5(-/-) mice exhibited smaller skeletons, particularly long bones, compared to Ifitm5(+/-) controls.
- The impact of Ifitm5 deficiency was more pronounced in newborn mice, suggesting a role in prenatal bone development.
- No significant differences in overall bone morphometric parameters were observed.
Conclusions:
- IFITM5 interacts with FKBP11 in osteoblasts, but its role in protein folding or immunosuppression binding remains unclear.
- IFITM5 deficiency impacts skeletal development, especially prenatal bone formation, though compensatory mechanisms may mitigate the effects.
- Further research is needed to elucidate the precise function of IFITM5 in bone homeostasis and the nature of compensatory pathways.
