Table 1.
Current mouse models of adrenocortical tumors and their limitations.
| Model | Gene | Promoter/driver | Adrenocortical phenotype | Limitation | Reference |
|---|---|---|---|---|---|
| Men1± | Men1 | Whole-body KO | Hyperplasia, adenoma, carcinoma (lack of tumor grade definition) | Multiple tumors | (19, 20) |
| Prkar1a2Δ/+ | Prkar1a | EIIA-Cre | No adrenal phenotype | No adrenal phenotype | (21) |
| tTA/X2AS | Prkar1a | Tet-Off system | Hyperplasia maintaining of X-zone | Technical limitations, reproducibility | (22) |
| AdKO | Prkar1a | 0.5 Akr1b7-Cre | Expansion of X-like zone with zona fasciculata features, autonomous corticosterone secretion | Late phenotype | (23) |
| Pde8b−/− | Pde8b | Whole-body KO | Mild hyperplasia | No adrenal-specific ablation | (24) |
| ΔCat | Ctnnb1 | 0.5 Akr1b7-Cre | Hyperplasia, adenoma and ectopic zona glomerulosa, hyperaldosteronism | Rare carcinomas | (25) |
| APC-KO | Apc | Sf1-Crelow | Hyperplasia progressed to microscopic and macroscopic adenomas | Progression to carcinoma was never observed | (26) |
| APC KO-H19ΔDMD | Apc Igf2/H19 ICR | Sf1-Crelow | Hyperplasia and adenomas, more severe phenotype than APC-KO mice | One carcinoma | (26) |
| PEPCK-IGF | Igf2 | Pepck-Igf2 | Hyperplasia | No adrenocortical tumors | (27) |
| ΔCat; AdIgf2 | Ctnnb1 Igf2 | 0.5 Akr1b7-Cre | Hyperplasia, adenoma, slight increased proliferation compared to ΔCat mice | Moderate effect on tumor progression | (28) |
| 0.5 Akr1b7-Igf2 | |||||
| 4.5 Scc-Igf2 | |||||
| Acdacd/acd; p53± | Acd, Tp53 | Increased development of ACC compared to Acdacd/acd | Multiple tumors | (29) | |
| Inhα/TAg | SV40 (large T antigen) | 6kb inhibinα-TAg | Malignant ACTs developing upon gonadectomy | Unrelated to human pathology | (30) |
| AdTAg | SV40 (large T antigen) | 0.5 Akr1b7-TAg | Rapidly evolving tumors | (31) | |
| YAC TR | NR5A1 | YAC transgene | Hyperplasia and tumors | Tumors with gonadal phenotype | (32) |
MEN1, multiple endocrine neoplasia type 1; Prkar1a, Protein kinase cAMP-dependent regulatory subunit type I alpha; Akr1b7, aldo-keto reductase family 1, member b7; Pde8b, phosphodiesterase 8b; Ctnnb1, catenin (cadherin-associated protein), beta 1; APC, adenomatous polyposis coli; KO, knockout; ICR, imprinting control region; PEPCK, phosphoenolpyruvate carboxykinase; IGF2, insulin-like growth factor 2; Acd, adrenocortical dysplasia; TP53, tumor protein P53; TAg, tumor antigen; SV40, simian virus 40; YAC, yeast artificial chromosome; Nr5a1, nuclear receptor subfamily; tTA/X2AS, transgenic mouse carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline responsive promoter; ΔCat, Catnblox(ex3) line x 0.5AkR1b7-Cre.