Table 1.

List of transgene-modified TRAMP mice with their phenotype and the potential therapeutic application

Targeted gene	Gene function	Knockout strategya	Phenotype	Therapeutic application	References
IKKα	Activation of NF-kB	Mutation that prevents IKKα activation	Prolonged tumor onset, decreased metastasis occurrence and delayed mortality	Pharmacologic regulation of either expression of maspin or inactivation of NF-kB	[40]
TGFβRII	Initiates the downstream TGFβ signaling cascade	DNTGFβRII expressed in epithelial cells	Appearance of early malignant changes	Administration of TGFβ. However, TGFβ is also an immunosuppressive cytokine. Hence, administration of TGFβ might exert opposing effects	[49]
TGFβRII	Initiates the downstream TGFβ signaling cascade	DNTGFβRII expressed in CD8+ and CD4+ T	Reduced tumor growth associated with enhanced tumor antigen-specific T cell responses	This strategy could be used in adoptive immunotherapy to render tumor-specific T cells less susceptible to TGFβ-mediated immunosuppression	[53]
TGFβ	Immunoregulatory cytokine	Crossing mice with floxed and null alleles of TGFβ1 (Tgfβ1f/n) with CD4-Cre mice	As above	Inhibition of TGFβ by specific monoclonal antibodies. However, systemic inhibition of TGFβ might favor tumor cell growth	[53]
TGFβ	Immunoregulatory cytokine	Crossing Tgfβ1f/n with Foxp3-Cre mice	No effects on tumor growth	As above	[53]
Klrk1	Codifies for NKG2D	Deletion of the exons 1b to 6 of NKG2D	Appearance of more aggressive tumors	Treatment with IFNα and IL-2 may result in in vivo expansion and activation of NK cells	[62]
TCRδ	Allows thymic selection of γδ T cells and antigen recognition	B6.129P2 Tcrdtm1Mom/J mice are deficient for γδ T cells	Appearance of more aggressive tumors	Zolendronate and IL-2 activate in vivo γδ T cells	[91]
Jα18	Allows thymic selection of iNKT cells and antigen recognition	B6.129-Tcra-Jtm1tg mice are deficient for iNKT cells	Appearance of more precocious and aggressive tumors	Treatment with αGalCer or αGalCer–modulated DC	[98]
IDO	Promotes the catabolism of tryptophan	Deletion of the exons 3–5 of the IDO gene	Delayed appearance of palpable tumor in TRAMP IDO−/− mice	Pharmacological inhibition of IDO by 1-methyl-tryptophan	[151]

^aTRAMP mice were crossed with mice carrying the indicated genetic alteration for several generations to generate TRAMP mice of nearly identical background and carrying the additional genetic alteration