title: The soluble type 2 insulin-like growth factor (IGF-II) receptor reduces organ size by IGF-II-mediated and IGF-II-independent mechanisms.
abstract: The soluble type 2 insulin-like growth factor (IGF) receptor or IGF-II/mannose 6-phosphate receptor (sIGF2R) is produced in vivo by proteolytic deletion of the transmembrane and intracellular domains of the cellular form of the receptor (IGF2R). There is evidence that sIGF2R is a negative regulator of growth. We have shown that transgenic mice expressing an Igf2r cDNA with a deleted transmembrane domain sequence (sDeltaIgf2r) show reduced local organ size. In the present study, we investigate whether sDeltaIGF2R can slow the growth induced by an excess of IGF-II and whether the biological activity of sDeltaIGF2R is due solely to its interactions with IGF-II. To this end, we crossed sDeltaIgf2r transgenics by mice overexpressing IGF-II (Blast line) or by mice carrying a disrupted paternal (active) allele of the Igf2 gene (Igf2(m+/p-)). Analysis of the phenotypes revealed that the soluble IGF2R affects the size of some organs (colon and cecum) exclusively by reducing the biological activity of IGF-II, whereas in other organs (stomach and skin) the biological activity of the receptor is at least in part independent of IGF-II and must involve an interaction with other factor(s).
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Silvio.Zaina@medforsk.mas.lu.se
authors.forename: S
authors.initials: S
authors.lastname: Zaina
authors.forename: S
authors.initials: S
authors.lastname: Squire
mesh_terms: D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D006579:Heterozygote; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010641:Phenotype; D017451:Receptors, Somatomedin / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II