Cellular availability of all-trans-retinoic acid in mice: a pilot study.
- 1Department of Anatomy and Embryology, Institute of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
- 2College of Medicine, School of Medicine and Health Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
- 3Laboratory Animal Resource Center, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Abstract
Retinoic acid signaling is essential for mammalian development and health. The genetic manipulations that enable visualization of this signal have revealed its involvement in many organs, including the eyes, colon, and trunk regions of mouse embryos. The in vivo cellular availability of the ligand, all-trans-retinoic acid (ATRA), is, however, still unclear, even though it, along with receptor expression, constitutes an essential part of signal transduction. In this pilot study, we sought to identify cells with ATRA availability by introducing a fusion protein comprising the mouse retinoic acid receptor alpha ligand-binding domain and the yeast Gal4 DNA-binding domain in mice. By crossing with other reporter mice with Gal4-responsive Cre expression and subsequent tandem DsRed expression to track ATRA availability through adulthood, we labeled the in vivo cellular availability of ATRA in two out of 14 mice from three F1-generation lines. As expected, we observed prior ATRA availability in organs associated with this signaling pathway, including the eye and colon. In addition, we observed prior ATRA availability in gastric epithelial cells and hepatocytes, which originates from the intestinal region where ATRA availability has not been determined, suggesting that ATRA's involvement in development or physiology may be greater than previously thought. Unfortunately, prior ATRA availability was limited to a small population of cells in the animals owing to low expression of the fusion receptor, as determined by quantitative reverse-transcription PCR. In summary, this pilot study suggested extensive effects of ATRA, underscoring its potential importance in developmental biology and clinical nutrition. In addition, this study encourages careful transgene design by reporting our experience with a low success rate in transgene expression.
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BibTeX
@article{yoshihara2026cellular,
title = {{Cellular availability of all-trans-retinoic acid in mice: a pilot study.}},
author = {Masaharu Yoshihara and Yoshitoku Watabe and Baoshuo Ning and Hayate Suzuki and Seiya Mizuno and Satoru Takahashi},
journal = {Biochemistry and biophysics reports},
year = {2026},
month = oct,
doi = {10.1016/j.bbrep.2026.102839},
url = {https://europepmc.org/article/MED/42926825},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cellular availability of all-trans-retinoic acid in mice: a pilot study.
AU - Masaharu Yoshihara
AU - Yoshitoku Watabe
AU - Baoshuo Ning
AU - Hayate Suzuki
AU - Seiya Mizuno
AU - Satoru Takahashi
PY - 2026
DA - 2026/10/15
JO - Biochemistry and biophysics reports
DO - 10.1016/j.bbrep.2026.102839
UR - https://europepmc.org/article/MED/42926825
AB - Retinoic acid signaling is essential for mammalian development and health. The genetic manipulations that enable visualization of this signal have revealed its involvement in many organs, including the eyes, colon, and trunk regions of mouse embryos. The in vivo cellular availability of the ligand, all-trans-retinoic acid (ATRA), is, however, still unclear, even though it, along with receptor expression, constitutes an essential part of signal transduction. In this pilot study, we sought to identify cells with ATRA availability by introducing a fusion protein comprising the mouse retinoic acid receptor alpha ligand-binding domain and the yeast Gal4 DNA-binding domain in mice. By crossing with other reporter mice with Gal4-responsive Cre expression and subsequent tandem DsRed expression to track ATRA availability through adulthood, we labeled the in vivo cellular availability of ATRA in two out of 14 mice from three F1-generation lines. As expected, we observed prior ATRA availability in organs associated with this signaling pathway, including the eye and colon. In addition, we observed prior ATRA availability in gastric epithelial cells and hepatocytes, which originates from the intestinal region where ATRA availability has not been determined, suggesting that ATRA's involvement in development or physiology may be greater than previously thought. Unfortunately, prior ATRA availability was limited to a small population of cells in the animals owing to low expression of the fusion receptor, as determined by quantitative reverse-transcription PCR. In summary, this pilot study suggested extensive effects of ATRA, underscoring its potential importance in developmental biology and clinical nutrition. In addition, this study encourages careful transgene design by reporting our experience with a low success rate in transgene expression.
SN - 2405-5808
ER -