RET(Men2B)-transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf-/- or gfr alpha-1(-/-) mice

Autor: Carolina Gestblom, Indrani Rajan, Raj P. Kapur
Rok vydání: 2002
Předmět:
Genetically modified mouse
Male
endocrine system
medicine.medical_specialty
Glial Cell Line-Derived Neurotrophic Factor Receptors
endocrine system diseases
Colon
Transgene
Adrenal Gland Neoplasms
Myenteric Plexus
Mice
Transgenic
Celiac Plexus
Multiple Endocrine Neoplasia Type 2b
Polymerase Chain Reaction
Pathology and Forensic Medicine
Mice
Internal medicine
Proto-Oncogene Proteins
medicine
Glial cell line-derived neurotrophic factor
Image Processing
Computer-Assisted
Missense mutation
Animals
Drosophila Proteins
Hirschsprung Disease
Multiple endocrine neoplasia
Mice
Knockout
biology
urogenital system
Kinase
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Ganglioneuroma
General Medicine
DNA
medicine.disease
Disease Models
Animal
Endocrinology
nervous system
Animals
Newborn
Pediatrics
Perinatology and Child Health
Cancer research
biology.protein
Acetylcholinesterase
Female
Multiple endocrine neoplasia type 2b
Zdroj: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 4(5)
ISSN: 1093-5266
Popis: Multiple endocrine neoplasia type 2B (MEN2B) syndrome is caused by a missense mutation in the RET gene, which replaces Met918 by Thr in the intracellular kinase domain of the protein. This single amino acid substitution transforms the receptor into a constitutively active monomeric kinase (RET(Men2B)) and produces an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies, and mucosal ganglioneuromas. The ligand, GDNF, stimulates RET activity through a co-receptor, GFR alpha-1. In vitro studies have shown that the kinase and mitogenic properties of RET(Men2B) are enhanced by GDNF/GFR alpha-1 stimulation. A relevant clinical question is whether ablation of either GDNF or GFR alpha-1 could alter penetrance or severity of the MEN2B syndrome. We report that ganglioneuromatous tumors caused by a RET(Men2B) transgene in mice are not affected grossly or microscopically by the absence of gdnf or gfr alpha-1. Loss-of-function mutations in ret, gdnf, or gfr alpha-1 cause pan-intestinal aganglionosis in mice. We find that expression of the RET(Men2B) transgene in enteric neural progenitors, after they colonize the gut, does not prevent intestinal aganglionosis associated with gdnf or gfr alpha-1 deficiency.
Databáze: OpenAIRE
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