Table 5 GEMMs described in literatures

Kit^V558Δ/+ Mice

Germ line deletion of V558 of Ex. 11 of mouse Kit gene. KIT V559 of Ex. 11 in human

Heterozygotes had cecal GIST with high penetrance, and showed diffuse ICC hyperplasia from oesophagus to large intestine

[299]

Kit^+/K641E:Neo mice Kit^{K641E:Neo/K641E:Neo} mice

Germ line K641E mutation at Ex. 13 of mouse Kit was introduced in mice. Corresponding to human KIT K642E mutation at Ex. 13

Both homozygotes and heterozygotes had cecal GIST and showed diffuse ICC hyperplasia from oesophagus to large intestine. Homozygotes died 30 weeks after birth. Heterozygotes have smaller GISTs

[300]

Kit^D818Y/+ mice Kit^D818Y/D818Y mice

Germ line Kit D818Y mutation was introduced in mice. Corresponding to human KIT D820Y mutation at Ex. 17

Both homozygotes and heterozygotes had cecal GIST and showed diffuse ICC hyperplasia from oesophagus to large intestine. Homozygotes had larger cecal tumor

[301]

Kit^{V558Δ;T669I/+} mice

Mouse Kit T669I mutation corresponding to human KIT T670I mutation. A mouse model for imatinib-resistant GIST

Mutant mice had a prolonged lifespan, developed smaller cecal GIST and more pronounced ICC hyperplasia in the stomach and colon, when compared to Kit^V558Δ/+ mice

[302]

Ptch^flox/flox-Lys^Mcre± mice

Cell specific loss of expression of Ptch from lysozyme M-expressing cells

About 82% mutant mice had GIST-liked tumors, which sometimes expressed Pdgfrα, but not Kit, arising from the wall of stomach or intestine

[303]

Etv1^flox/flox; Kit^Δ558V/+; Rosa26^{CreERT2/CreERT2} mice

Inducible Etv1 knockout mice, suitable for the study of the function of Etv1 in GIST

Vehicle-treated mice had an identical phenotype to the Kit^Δ558V/+ mice, with GIST-like tumors in cecum and ICC hyperplasia in large intestine and stomach

[304]

Kit^{V558Δ; Y567F/Y567F} mice

The KIT phosphorylation site was blocked by introducing Y567F mutation

Mutant mice had similar but significantly smaller cecal GIST to that of Kit^V558Δ/+ mice, had less ICC hyperplasia in stomach and colon

[305]

Etv1^CreERT2; Braf ^CA/+; Trp53^fl/fl mice

A mouse model of aggressive imatinib-resistant human BRAF^V600E-mutant GIST

Mutant mice developed ICC hyperplasia and multifocal GIST-like tumors within the gastrointestinal tract with 100% penetrance after the tamoxifen administration

[306]

Lrig1^CreERT2/+; Braf^{LSL−V600E/+} mice

Mutant Braf expression could be induced in Lrig1 expressing cells

Activation of mutant Braf in mice resulted in oral tumors (squamous papillomas), and ICC hyperplasia in mouse stomach and colon

[307]

Myh11^CreERT2; Braf^{LSL−V600E/+} mice

Mutant Braf expression could be induced in Myh11 expressing smooth muscle cells

Approximately 36.4% mice showed overt GIST either in stomach, cecum or bladder. ICC hyperplasia was also found in mutant mice

[307]

Lrig1^CreERT2/+; Rosa^LSL−Kitc/+ mice

Mutant KIT expression could be induced in Lrig1 expressing cells

Mutant mice developed small GIST-like lesions in the muscularis propria of the stomach and intestine

[307]

Kit^{V558Δ;V653A−NEO/+}; Etv1^Cre−ERT2/+ mice

Corresponding to human KIT V654A mutation, a model of imatinib resistant GIST caused by secondary mutation

More than 95% mice developed cecal GIST after tamoxifen administration. Mutant mice had larger tumors and decreased survival when compared to Kit^V558Δ/+ mice

[308]