Related Experiment Video
Updated: Aug 18, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret
A Schuchardt1, V D'Agati, L Larsson-Blomberg
1Department of Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Abstract:
Receptor tyrosine kinases (RTKs) are cell-surface molecules that transduce signals for cell growth and differentiation. The RTK encoded by the c-ret proto-oncogene is rearranged and constitutively activated in a large proportion of thyroid papillary carcinomas, and germ-line point mutations in c-ret seem to be responsible for the dominantly inherited cancer syndromes multiple endocrine neoplasia (MEN) types 2A and B. The gene is expressed in the developing central and peripheral nervous systems (sensory, autonomic and enteric ganglia) and the excretory system (Wolffian duct and ureteric bud epithelium) of mice, indicating that it may play a role in normal development. Here we show that mice homozygous for a targeted mutation in c-ret develop to term, but die soon after birth, showing renal agenesis or severe dysgenesis, and lacking enteric neurons throughout the digestive tract. Ret is thus an essential component of a signalling pathway required for renal organogenesis and enteric neurogenesis.
Insights
The c-ret proto-oncogene is essential for kidney development and the formation of enteric neurons. Mice lacking functional c-ret die shortly after birth due to severe kidney defects and lack of gut innervation.
Area of Science:
- Developmental Biology
- Neuroscience
- Oncology
Background:
- Receptor tyrosine kinases (RTKs) regulate cell growth and differentiation.
- The c-ret proto-oncogene is implicated in thyroid cancer and inherited cancer syndromes.
- c-ret is expressed in developing nervous and excretory systems, suggesting a role in normal development.
Purpose of the Study:
- To investigate the role of the c-ret proto-oncogene in mammalian development.
- To determine the function of Ret signaling in renal and enteric neurogenesis.
Main Methods:
- Generation of mice with a targeted mutation in the c-ret gene.
- Analysis of homozygous mutant mice for developmental defects.
Main Results:
- Mice homozygous for the c-ret mutation were born but died perinatally.
- Mutant mice exhibited renal agenesis or severe dysgenesis.
- A complete absence of enteric neurons was observed throughout the digestive tract.
Conclusions:
- Ret signaling is crucial for proper renal organogenesis.
- Ret signaling is essential for the development of enteric neurons.
- The c-ret proto-oncogene plays a vital role in both kidney and gut development.
Related Concept Videos
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:16In-vitro Mutagenesis
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...