A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Approval
2.2. Animal Models
2.3. Animal Treatments
2.4. Immunohistochemistry
2.5. Real-Time PCR
2.6. T2 MRI Scan
2.7. Statistical Analysis
3. Results
3.1. Administration of TNKSi Attenuates WNT Pathway Activity In Vivo and Partially Rescues Cranial Defects In Vivo
3.2. In Vivo Administration of TNKSi Results in Live Births of Apcmin/flox Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitor | Treatment | Outcome |
---|---|---|
None | NA | All progeny Apcflox/+ (15/15, born alive, 5 litters) |
G007-LK | E5–14 | Complete abortion (no embryonic tissue detected at E15; 1 pregnancy) |
G007-LK | E2–3 | Complete abortion (no embryonic tissue detected at E15; 1 pregnancy) |
G007-LK | E5–10 | Complete abortion (no embryonic tissue detected at E15; 1 pregnancy) |
G007-LK | E4–7 | Complete abortion (no embryonic tissue detected at E15; 1 pregnancy) |
G007-LK | E5–6 | Deformed, non-viable embryos (3/3; E15, 1 litter, genotypes not determined) |
G007-LK | E5–7 | Rescue of headless phenotype in subset (5/8) of Apcmin/flox embryos (E15, 2 litters, 17 embryos in total: 9 Apcflox/+, 8 Apcmin/flox) |
G007-LK | E5–7 & E9–10 | Complete abortion (no embryonic tissue detected at E15; 1 pregnancy) |
G007-LK | E5–7 | Rescue of headless phenotype in subset (8/11) of born pups (3 litters, 19 pups in total: 8 Apcflox/+, 11 Apcmin/flox) |
Pyrvinium | E5–7 | Rescue of headless phenotype in subset (1/3) of born pups (1 litter, 4 pups in total: 1 Apcflox/+, 3 Apcmin/flox) |
Born Alive | Stillborn | |||||
---|---|---|---|---|---|---|
Drug | Genotype | Two Eyes | One Eye | No Eye | Cranial Defects | Litters (n) |
none | flox/+ | 15 | 0 | 0 | 0 | 5 |
none | min/flox | 0 | 0 | 0 | 0 | |
G007-LK | flox/+ | 7 | 1 | 0 | 0 | 3 |
G007-LK | min/flox | 0 | 3 | 5 | 3 | |
Pyrvinium | flox/+ | 1 | 0 | 0 | 0 | 1 |
Pyrvinium | min/flox | 0 | 0 | 1 | 2 |
Treatment | Anophthalmia | Normal | Total |
---|---|---|---|
WNT antagonist | 10 | 8 | 18 |
None | 0 | 15 | 15 |
Total | 10 | 23 | 33 |
Study Parameters | |
---|---|
Anophthalmia incidence (sporadic), group 1 | 4.3% |
Anophthalmia incidence (treatment-induced), group 2 | 55.6% |
Alpha | 0.05 |
Beta | 0.2 |
Power | 0.8 |
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Tse, J.; O’Keefe, R.; Rigopolous, A.; Carli, A.L.E.; Waaler, J.; Krauss, S.; Ernst, M.; Buchert, M. A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors. Biomedicines 2023, 11, 2719. https://doi.org/10.3390/biomedicines11102719
Tse J, O’Keefe R, Rigopolous A, Carli ALE, Waaler J, Krauss S, Ernst M, Buchert M. A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors. Biomedicines. 2023; 11(10):2719. https://doi.org/10.3390/biomedicines11102719
Chicago/Turabian StyleTse, Janson, Ryan O’Keefe, Angela Rigopolous, Annalisa L. E. Carli, Jo Waaler, Stefan Krauss, Matthias Ernst, and Michael Buchert. 2023. "A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors" Biomedicines 11, no. 10: 2719. https://doi.org/10.3390/biomedicines11102719
APA StyleTse, J., O’Keefe, R., Rigopolous, A., Carli, A. L. E., Waaler, J., Krauss, S., Ernst, M., & Buchert, M. (2023). A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors. Biomedicines, 11(10), 2719. https://doi.org/10.3390/biomedicines11102719