KIT is required for hepatic function during mouse post-natal development

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...

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Bibliographic Details
Published in:BMC developmental biology 2007-07, Vol.7 (1), p.81-81, Article 81
Main Authors: 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, de Angelis, Martin Hrabe, Hérault, Yann
Format: Article
Language:English
Subjects:
Alleles
Anemia
Anemia - genetics
Anemia - metabolism
Animal development
Animals
Animals, Newborn
Chemical properties
Evaluation
Fatty Liver
Fatty Liver - genetics
Fatty Liver - metabolism
Fetal Stem Cells
Fetal Stem Cells - metabolism
Gene Expression Regulation, Developmental
Genetic aspects
Hematopoiesis
Immunology
Life Sciences
Lipid Metabolism
Lipid Metabolism - genetics
Liver
Liver - embryology
Liver - growth & development
Liver - metabolism
Liver cells
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mutation
Phenotype
Physiological aspects
Properties
Protein tyrosine kinase
Proto-Oncogene Proteins c-kit
Proto-Oncogene Proteins c-kit - genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
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Description
Summary: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. 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. 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.
ISSN:1471-213X
1471-213X
DOI:10.1186/1471-213x-7-81