ArticleProceedings of the National Academy of Sciences of the United States of America2000
Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- The IGF signaling axis in thyroid cancer: biological complexity and therapeutic challenges.Endocrine connections · 2026Review
- Depletion of IGFALS Serum Level up to 3 Months After Cardiac Surgery, with Exploration of Potential Relationships to Surrogates of Organ Failures and Clinical Outcomes.Current issues in molecular biology · 2025Article
- Insulin-Like Growth Factor Binding Protein, Acid-Labile Subunit Serum Level During the Acute and Convalescent Stage of SARS-CoV-2 Infection Depicted in a Longitudinal Study of 72 Patients During the First Wave of Pandemic.Journal of multidisciplinary healthcare · 2025Article
- Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.Nature reviews. Endocrinology · 2024Review
- Plasma Proteomic Analysis Reveals the Potential Role of Lectin and Alternative Complement Pathways in IgA Vasculitis Pathogenesis.Diagnostics (Basel, Switzerland) · 2023Article
- Insulin signaling in the long-lived reproductive caste of ants.Science (New York, N.Y.) · 2022Article
- Mice with gene alterations in the GH and IGF family.Pituitary · 2022Review
- Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach.Scientific reports · 2021Article
- Insulin-like growth factors: Ligands, binding proteins, and receptors.Molecular metabolism · 2021Review
- Review
- Mouse models of growth hormone insensitivity.Reviews in endocrine & metabolic disorders · 2021Review
- Effects of GH/IGF axis on bone and cartilage.Molecular and cellular endocrinology · 2021Review
- The Actions of IGF-1 in the Growth Plate and Its Role in Postnatal Bone Elongation.Current osteoporosis reports · 2020Review
- An internal deletion of ADAR rescued by MAVS deficiency leads to a minute phenotype.Nucleic acids research · 2020Article
- Neuron-specific Mafb knockout causes growth retardation accompanied by an impaired growth hormone/insulin-like growth factor I axis.Experimental animals · 2019Article
- Nonclassical GH Insensitivity: Characterization of Mild Abnormalities of GH Action.Endocrine reviews · 2019Review
- Differential tissue response to growth hormone in mice.FEBS open bio · 2018Article
- Insulin-like growth factors: actions on the skeleton.Journal of molecular endocrinology · 2018Review
- Extensive phenotypic characterization of a new transgenic mouse reveals pleiotropic perturbations in physiology due to mesenchymal hGH minigene expression.Scientific reports · 2017Article
- Comparison of pulsatile vs. continuous administration of human placental growth hormone in female C57BL/6J mice.Endocrine · 2016Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Insulin-like growth factors (IGFs) I and II are important regulators of cell proliferation and differentiation. After birth, plasma IGFs, representing mostly liver-derived IGFs, circulate in ternary complexes of 150 kDa consisting of one molecule each of IGF, IGF-binding protein (IGFBP) 3, and an acid labile subunit (ALS). Onset of ALS synthesis after birth is the primary factor driving the formation of ternary complexes. Capture of IGFs by ALS is thought to allow the development of a plasma reservoir without negative effects such as hypoglycemia and cell proliferation. To evaluate the importance of ALS and ternary complexes, we have created mice in which the ALS gene has been inactivated. The mutation was inherited in a Mendelian manner, without any effects on survival rates and birth weights. A growth deficit was observed in null mice after 3 weeks of life and reached 13% by 10 weeks. This modest phenotype was observed despite reductions of 62 and 88% in the concentrations of plasma IGF-I and IGFBP-3, respectively. Increased turnover accounted for these reductions because indices of synthesis in liver and kidney were not decreased. Surprisingly, absence of ALS did not affect glucose and insulin homeostasis. Therefore, ALS is required for postnatal accumulation of IGF-I and IGFBP-3 but, consistent with findings supporting a predominant role for locally produced IGF-I, is not critical for growth. This model should be useful to determine whether presence of ALS is needed for other actions of liver-derived IGF-I and for maintenance of homeostasis in presence of high circulating levels of IGF-II.
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