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Overexpression of human insulin-like growth factor-II in transgenic mice causes increased growth of the thymus.
van Buul-Offers, S C; de Haan, K; Reijnen-Gresnigt, M G; Meinsma, D; Jansen, M; Oei, S L; Bonte, E J; Sussenbach, J S; Van den Brande, J L.
Afiliação
  • van Buul-Offers SC; Department of Pediatrics, Wilhelmina Children's Hospital, The Netherlands.
J Endocrinol ; 144(3): 491-502, 1995 Mar.
Article em En | MEDLINE | ID: mdl-7537791
In order to determine the effects of IGF-II overexpression on growth of mice, transgenic mice were produced carrying one of three different H-2Kb human IGF-II minigenes in which different non-coding exons (exon 5, truncated exon 5 or exon 6) preceded the coding exons 7, 8 and 9. These were spaced by truncated introns and for proper polyadenylation an SV40 polyadenylation signal was incorporated. The highest levels of IGF-II minigene mRNA expression were found in lines containing the truncated exon 5 construct (II5'). Those containing exon 6 (II6) had less expression and 5 constructs (II5) gave only moderate levels of mRNA expression. In general mRNA expression was highest in thymus and spleen, low in liver and kidney and absent in the brain. In addition, one II5' line showed expression in the brain. Serum IGF-II levels at 8 weeks of age were increased 7- to 8-fold in homozygous transgenic lines with construct II5' without brain expression and 2- to 3-fold in the one that showed expression in the brain; serum IGF-I levels were unchanged. Serum IGFs in the lines containing the constructs II5 and II6 were not different from those of the controls. In all cases body length and weight as well as the weight of several organs such as brain, liver, kidneys, heart and spleen when expressed as a function of age did not differ from controls. Only the thymus showed a significant increase in weight in the transgenics II5'. Inbreeding of 2 lines containing construct II5' with pituitary deficient Snell dwarf mice did not influence body length or weight despite increased serum IGF-II levels. Again the thymus showed a marked increase in growth. The biological activity of the IGF-II peptide was further demonstrated by increased serum IGF-binding protein-3 in the transgenic dwarf mice, as shown by Western ligand blotting. In summary, overexpression of IGF-II in transgenic normal and dwarf mice does not affect overall body growth, but causes increased growth of the thymus. This suggests a role for IGF-II in thymic development by paracrine/autocrine action.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Timo / Fator de Crescimento Insulin-Like II / Camundongos Transgênicos Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Endocrinol Ano de publicação: 1995 Tipo de documento: Article País de afiliação: Holanda
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Timo / Fator de Crescimento Insulin-Like II / Camundongos Transgênicos Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Endocrinol Ano de publicação: 1995 Tipo de documento: Article País de afiliação: Holanda