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Versatile and enhanced tumour modelling in mice via somatic cell transduction.

Rodriguez E, Mannion L, D'Santos P, Griffiths M, Arends MJ, Brindle KM, Lyons SK - J. Pathol. (2014)

Bottom Line: The vectors deliver a tamoxifen-inducible and self-inactivating Cre recombinase, conditional bioluminescent and fluorescent proteins and an shRNA component.We also show that a variant vector expressing shRNA alters tumour growth dynamics and the histological grade associated with the inherited genotype.They should also be useful for inducing imageable tumours in organs other than the lung, provided that the inherited conditional genotype is sufficiently penetrant.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Imaging, CRUK Cambridge Institute, University of Cambridge, UK.

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(a) Lentiviral miR variant construct (LV–indLS2miR1224) before and after tamoxifen administration. (b) Longitudinal analysis of tumour development in K, KP, K+miR and wild-typemice after infection with LV–indLS2 or LV–indLS2miR1224. Each symbol corresponds to an individual animal. Bioluminescence emission (photons/s/cm2/sr) on y axis and time (days) on x axis. (c) Longitudinal BLI of Kras mice following infection with LV–indLS2miR1224
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fig03: (a) Lentiviral miR variant construct (LV–indLS2miR1224) before and after tamoxifen administration. (b) Longitudinal analysis of tumour development in K, KP, K+miR and wild-typemice after infection with LV–indLS2 or LV–indLS2miR1224. Each symbol corresponds to an individual animal. Bioluminescence emission (photons/s/cm2/sr) on y axis and time (days) on x axis. (c) Longitudinal BLI of Kras mice following infection with LV–indLS2miR1224

Mentions: The measured lung bioluminescence from K mice transduced with LV-indLSmiR1224 developed in a manner intermediate to that of to its inherited genotype and KP mice (Figure 3). Unambiguous lung signal appeared approximately 1 month earlier in this cohort than in K or KP mice, however; once bioluminescence was established (after ˜100 days), the tumours did not appear to develop as quickly as those from the KP cohort. Histological analysis of lung tumours from these mice (Figures 4, S4, S5 and Table1) at 7 months post-Cre induction showed that the tumour phenotype was broadly similar, but intermediate in terms of grade, to mice with inherited K and KP genotypes. In addition to developing tumours faster than K mice, K+mir1224 mice developed more frequent high-grade adenomas, but not as frequently as KP mice.


Versatile and enhanced tumour modelling in mice via somatic cell transduction.

Rodriguez E, Mannion L, D'Santos P, Griffiths M, Arends MJ, Brindle KM, Lyons SK - J. Pathol. (2014)

(a) Lentiviral miR variant construct (LV–indLS2miR1224) before and after tamoxifen administration. (b) Longitudinal analysis of tumour development in K, KP, K+miR and wild-typemice after infection with LV–indLS2 or LV–indLS2miR1224. Each symbol corresponds to an individual animal. Bioluminescence emission (photons/s/cm2/sr) on y axis and time (days) on x axis. (c) Longitudinal BLI of Kras mice following infection with LV–indLS2miR1224
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288983&req=5

fig03: (a) Lentiviral miR variant construct (LV–indLS2miR1224) before and after tamoxifen administration. (b) Longitudinal analysis of tumour development in K, KP, K+miR and wild-typemice after infection with LV–indLS2 or LV–indLS2miR1224. Each symbol corresponds to an individual animal. Bioluminescence emission (photons/s/cm2/sr) on y axis and time (days) on x axis. (c) Longitudinal BLI of Kras mice following infection with LV–indLS2miR1224
Mentions: The measured lung bioluminescence from K mice transduced with LV-indLSmiR1224 developed in a manner intermediate to that of to its inherited genotype and KP mice (Figure 3). Unambiguous lung signal appeared approximately 1 month earlier in this cohort than in K or KP mice, however; once bioluminescence was established (after ˜100 days), the tumours did not appear to develop as quickly as those from the KP cohort. Histological analysis of lung tumours from these mice (Figures 4, S4, S5 and Table1) at 7 months post-Cre induction showed that the tumour phenotype was broadly similar, but intermediate in terms of grade, to mice with inherited K and KP genotypes. In addition to developing tumours faster than K mice, K+mir1224 mice developed more frequent high-grade adenomas, but not as frequently as KP mice.

Bottom Line: The vectors deliver a tamoxifen-inducible and self-inactivating Cre recombinase, conditional bioluminescent and fluorescent proteins and an shRNA component.We also show that a variant vector expressing shRNA alters tumour growth dynamics and the histological grade associated with the inherited genotype.They should also be useful for inducing imageable tumours in organs other than the lung, provided that the inherited conditional genotype is sufficiently penetrant.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Imaging, CRUK Cambridge Institute, University of Cambridge, UK.

Show MeSH
Related in: MedlinePlus