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Abstract
During embryogenesis, various ligand-receptor interactions take place to modulate
the development and growth of various mammalian organs. During these interactions,
a critical concentration of a given receptor is needed to elicit a ligand-induced
biologic response at a defined gestational stage of the fetus. In this study, the
distribution and the relevance of insulin-like growth factor-I receptor (IGF-IR) in
metanephric development was investigated. Kidneys were harvested from mouse embryos
at days 13 to 19 of fetal gestation, and maintained in a metanephric culture system.
Immunofluorescence studies, using anti-IGF-IR, revealed a high expression of IGF-IR
at day 13, which declined during the later stages of gestation through neonatal life.
To study the relevance of IGF-IR expression in metanephric development, antisense-oligodeoxynucleotide
(ODN) experiments were carried out. Antisense-ODN 43 mer probes were synthesized utilizing
rat IGF-IR cDNA selected nucleotide sequences which are highly conserved in other
mammalian species. Southern blot analyses of various restriction fragments of the
rat and mice genomic DNA yielded similar bands when hybridized with the antisense-ODN
or rat IGF-IR cDNA, suggesting a high degree of homology in the region of the gene
selected for the synthesis of antisense-ODN. Also, the antisense-ODN hybridized with
the appropriate murine fetal kidney mRNA species, as ascertained by S1 nuclease protection
assay. Inclusion of antisense-ODN in the culture medium resulted in an inhibition
of the growth of the kidney, reduction in the population of the nephrons and disorganization
of the ureteric bud branches.(ABSTRACT TRUNCATED AT 250 WORDS)