KIT is required for hepatic function during mouse post-natal development
2007
Magnol, Laetitia | Chevallier, Marie-Clémence | Nalesso, Valérie | Retif, Stéphanie | Fuchs, Helmut | Klempt, Martina | Pereira, Patricia | Riottot, Michel | Andrzejewski, Sandra | Doan, Bich-Thuy | Panthier, Jean-Jacques | Puech, Anne | Beloeil, Jean-Claude | Hrabe de Angelis, Martin | Hérault, Yann
Background: The Kit gene encodes a receptor tyrosine kinase involved in various biological processes including melanogenesis, hematopoiesis and gametogenesis in mice and human. A large number of Kit mutants has been described so far showing the pleiotropic phenotypes associated with partial loss-of-function of the gene. Hypomorphic mutations can induce a light coat color phenotype while complete lack of KIT function interferes with embryogenesis. Interestingly several intermediate hypomorphic mutations induced in addition growth retardation and post-natal mortality.[br/]Results: In this report we investigated the post-natal role of Kit by using a panel of chemically-induced hypomorphic mutations recently isolated in the mouse. We found that, in addition to the classical phenotypes, mutations of Kit induced juvenile steatosis, associated with the downregulation of the three genes, VldlR, Lpin1 and Lpl, controlling lipid metabolism in the post-natal liver. Hence, Kit loss-of-functions mimicked the inactivation of genes controlling the hepatic metabolism of triglycerides, the major source of energy from maternal milk, leading to growth and viability defects during neonatal development.[br/]Conclusion: This is a first report involving KIT in the control of lipid metabolism in neonates and opening new perspectives for understanding juvenile steatosis. Moreover, it reinforces the role of Kit during development of the liver and underscores the caution that should be exerted in using KIT inhibitors during anti-cancer treatment.
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