Reference SummaryKwak MK, PLoS One 2013;8(1):e53476

Title

 Conditional deletion of the Pten gene in the mouse prostate induces prostatic intraepithelial neoplasms at early ages but a slow progression to prostate tumors.

Authors

 Kwak MK; Johnson DT; Zhu C; Lee SH; Ye DW; Luong R; Sun Z

Journal

 PLoS One

Volume

 8

Issue

 1

Year

 2013

Pages

 e53476

Abstract

 The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, Pten(LoxP):Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of Pten(LoxP/LoxP):Osr1-Cre mice as early as 2 weeks of age. Intriguingly, Pten(LoxP/LoxP):Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. Pten(LoxP/+):Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of Pten(LoxP/LoxP):Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated Pten(LoxP/LoxP):Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate.

Links

 J:195810 – MGI References
23308230 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.Cg These mice were generated by crossing C;129-Ptentm1Hwu and FVB/N-Tg(Osr1-cre)4Mrt. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.
B6.Cg-Ptentm1Hwu These mice were generated by crossing C;129-Ptentm1Hwu and FVB/N-Tg(Osr1-cre)4Mrt. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.
B6.Cg-Ptentm1Hwu/+ These mice were generated by crossing C;129-Ptentm1Hwu and FVB/N-Tg(Osr1-cre)4Mrt. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt These mice were generated by crossing C;129-Ptentm1Hwu and FVB/N-Tg(Osr1-cre)4Mrt. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt These mice were generated by crossing C;129-Ptentm1Hwu and FVB/N-Tg(Osr1-cre)4Mrt. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.
B6.Cg-Ptentm1Hwu Tg(Pbsn-cre)4Prb These mice were generated by crossing C;129-Ptentm1Hwu and B6;D2-Tg(Pbsn-cre)4Prb. The F1 progeny from that cross were subsequently backcrossed for more than 5 generations to C57BL/6J. Backcrossed mice were then intercrossed to generate the various genotypes used.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Lung carcinoma Lung

3.7
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Mammary gland adenocarcinoma Mammary gland

9.4
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Mesodermal cell/mesoblast sarcoma Gastrointestinal tract

6.25
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt PNS - Nerve sheath tumor - malignant PNS - Nerve sheath

3.7
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland - Anterior lobe prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland - Anterior lobe

100
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland - Dorsolateral lobe

100
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland - Ventral lobe prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland - Ventral lobe

100
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland adenocarcinoma - well-differentiated Prostate gland

12.5
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland carcinoma Prostate gland

62.5
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt Prostate gland carcinoma Prostate gland

0
B6.Cg-Ptentm1Hwu Prostate gland carcinoma Prostate gland

0
B6.Cg-Ptentm1Hwu/+ Prostate gland carcinoma Prostate gland

0
B6.Cg Prostate gland carcinoma Prostate gland

0
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland carcinoma - solid Prostate gland

50
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt Prostate gland hyperplasia Prostate gland

25
B6.Cg-Ptentm1Hwu Prostate gland hyperplasia Prostate gland

0
B6.Cg-Ptentm1Hwu/+ Prostate gland hyperplasia Prostate gland

0
B6.Cg Prostate gland hyperplasia Prostate gland

0
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland lesion Prostate gland

0
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt Prostate gland lesion Prostate gland

0
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

29 - 87.5
B6.Cg-Ptentm1Hwu Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

0
B6.Cg-Ptentm1Hwu/+ Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

0
B6.Cg Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

0
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland

100
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland prostatic intraepithelial neoplasia - high grade (HGPIN)
  • castration
 Prostate gland

100
B6.Cg-Ptentm1Hwu/+ Tg(Osr1-cre)4Mrt Prostate gland prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland

37.5 - 62.5
B6.Cg-Ptentm1Hwu Tg(Pbsn-cre)4Prb Prostate gland prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland

observed
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland tumor Prostate gland

0
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt Prostate gland tumor
  • castration
 Prostate gland

observed
B6.Cg-Ptentm1Hwu Tg(Osr1-cre)4Mrt (Unspecified organ) cystadenoma - papillary (Unspecified organ)

3.7