Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis AMice carrying null mutations of the genes encoding insulin-like growth factor-I (IGF-1) and type-1 IGF receptor (IGF1r). Cell 75: 59-72

Department of Genetics and Development, Columbia University, New York, New York 10032.
Cell (Impact Factor: 32.24). 11/1993; 75(1):59-72. DOI: 10.1016/S0092-8674(05)80084-4
Source: PubMed


Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf-2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.

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    • "Via their respective receptors, these stimuli converge on downstream pathways controlling the induction of adaptive gene programs and protein synthesis, and direct cellular metabolism and energy production. Well-characterized cascades and pathways regulating these homeostatic mechanisms comprise phosphoinositide 3 kinase (PI3K)/AKT, mTOR complex 1 (mTORC1), ERK1/2 and AMP-activated protein kinase (AMPK) (Baker et al., 1993; Liu et al., 1993; McMullen et al., 2003; Seth et al., 2009; Bostrom et al., 2010; Zhang et al., 2010). Translating stretch-stimuli to downstream signaling, the mechanosensing apparatus is controlled by transient receptor potential (TRP) channels, integrins and various z-disc associated proteins such as muscle LIM protein (MLP), actinin-associated LIM protein (ALP) and Nebulette (NEB) as well as the sarcomere-spanning protein titin (Linke, 2008; Seth et al., 2009; Frank and Frey, 2011; Luedde et al., 2011; Hamdani et al., 2013; Maillet et al., 2013). "
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    Development 03/2015; 142(5):817-831. DOI:10.1242/dev.105536 · 6.46 Impact Factor
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    • "Although fetal circulating IGF-II levels are higher throughout gestation, only free circulating IGF-I concentrations have consistently been shown to be reduced in FGR (Lassarre et al. 1991; Cianfarani et al. 1998). A 40 % decrease in fetal weight observed in IGF-I knockout mice with increased neonatal death provides a dramatic illustration of the critical role of IGF-I in normal fetal growth (Liu et al. 1993; Baker et al. 1993). IGF-I primarily exists in circulation bound to IGFBPs, and the endocrine responses of IGF-I are primarily mediated by binding to the IGF1 receptor (IGF1R). "
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