A mouse model of a human multiple GIST family with KIT-Asp820Tyr mutation generated by a knock-in strategy.

摘要: Several families exhibiting multiple gastrointestinal stromal tumours (GISTs) and germline c-kit gene mutations at exons 8, 11, 13, or 17 have been reported. These patients also exhibit diffuse hyperplasia of the interstitial cells Cajal (ICCs) as a pre-existing lesion GISTs. We generated mouse model family with mutation exon 17, compared phenotypes between mice humans. The counterpart (KIT-Asp818Tyr) human KIT-Asp820Tyr was transmitted into by knock-in strategy. Mating male female heterozygotes (KIT-Asp818Tyr/+) resulted in generation homozygotes (KIT-Asp818Tyr/KIT-Asp818Tyr). Histological examination revealed that all had both small KIT-positive mesenchymal tumour caecum, consistent GIST, spindle-shaped cell proliferation distal oesophagus, stomach, proximal duodenum, colon ICC hyperplasia. All exhibited larger caecal more prominent heterozygous mice, they usually died within 10 weeks after birth, likely due to ileus. intestine genotypes showed no apparent morphological abnormality, autonomous contraction ileal segments appeared normal. Western blotting demonstrated expressed phosphorylated KIT, MAPK, Stat1, Stat5. mutant are considered be useful for further investigation mechanism GIST development result assessment vivo effects drugs against molecular targets.