Partial correction of the dwart phenotype by non-viral transfer of the growth hormone gene in mice: treatment age is critical
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Growth Hormone and IGF Research
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Non-viral transfer of the growth hormone gene to different muscles of immunodeficient dwarf (lit/scid) mice is under study with the objective of improving phenotypic correction via this particular gene therapy approach. Plasmid DNA was administered into the exposed quadriceps or non-exposed tibialis cranialis muscle of lit/scid mice followed by electroporation, monitoring several growth parameters. In a 6-month bioassay, 50 μg DNA were injected three times into the quadriceps muscle of 80-day old mice. A 50% weight increase, with a catch-up growth of 21%, together with a 16% increase for nose-to-tail and tail lengths (catch-up = 19–21%) and a 24–28% increase for femur length (catch-up = 53–60%), were obtained. mIGF1 serum levels were ~ 7-fold higher than the basal levels for untreated mice, but still ~ 2-fold lower than in non-dwarf scid mice. Since treatment age was found to be particularly important in a second bioassay utilizing 40-day old mice, these pubertal mice were compared in a third bioassay with adult (80-day old) mice, all treated twice with 50 μg DNA injected into each tibialis cranialis muscle, via a less invasive approach. mIGF1 concentrations at the same level as co-aged scid mice were obtained 15 days after administration in pubertal mice. Catch-up growth, based on femur length (77%), nose-to-tail (36%) and tail length (39%) increases was 40 to 95% higher than those obtained upon treating adult mice. These data pave the way for the development of more effective pre-clinical assays in pubertal dwarf mice for the treatment of GH deficiency via plasmid-DNA muscular administration.
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HIGUTI, ELIZA; CECCHI, CLAUDIA R.; OLIVEIRA, NELIO A.J.; LIMA, ELIANA R.; VIEIRA, DANIEL P.; AAGAARD, LARS; JENSEN, THOMAS G.; JORGE, ALEXANDER A.L.; BARTOLINI, PAOLO; PERONI, CIBELE N. Partial correction of the dwart phenotype by non-viral transfer of the growth hormone gene in mice: treatment age is critical. Growth Hormone and IGF Research, v. 26, p. 1-7, 2016. Disponível em: http://repositorio.ipen.br/handle/123456789/25800. Acesso em: 30 Jun 2026.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.