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Gene Review

Igfals  -  insulin-like growth factor binding protein...

Mus musculus

Synonyms: ALS, Albs, Als, Insulin-like growth factor-binding protein complex acid labile subunit, mKIAA4111
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Disease relevance of Igfals


Psychiatry related information on Igfals


High impact information on Igfals

  • Lack of apoptosis in mice with ALS [7].
  • In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS) [8].
  • Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively [8].
  • Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis [8].
  • Thus, triggering of a motoneuron-restricted cell death pathway by neighboring cells might contribute to motoneuron loss in ALS [9].

Chemical compound and disease context of Igfals

  • Within 7 days post-AL, ALS/Lt mice exhibited hyperglycemia and hypoinsulinemia, whereas ALR/Lt mice maintained normal plasma insulin and glucose levels [10].
  • To evaluate the causative role of environmental aluminum (Al) in the development of neurodegeneration in Kiiamyotrophic lateral sclerosis (ALS), we examined how chronic exposure to a low-Ca/Mg and high-Al diet induced neuronal loss and tau-related neuronal degeneration in experimental animals [11].

Biological context of Igfals


Anatomical context of Igfals


Associations of Igfals with chemical compounds

  • By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule [17].
  • INTERPRETATION: The previously documented role of Cox-2 in ALS neurodegeneration in this particular mouse model occurs through a mechanism independent of prostaglandin E(2) [18].
  • Cultured ALS/Lt islets exposed for 5 min to increasing (0-3 mmol/l) AL concentrations in vitro exhibited an 80% decline in numbers of intact islets after a subsequent 6-day culture period, as well as a 75% reduction in islet insulin content and a 94% decrease in glucose-stimulated insulin secretory capacity [10].
  • However, pretreatment of the latter two strains with appropriate doses of either x-irradiation (150 R), cyclophosphamide (100 mg/kg) or ALS (150 mul) before carrier-preimmunization strikingly enhances the magnitude of IgE antibody responses in such mice to levels as high as 64-fold above those of untreated control mice of the same strains [19].
  • These manipulations included the use of pretransplant donor-specific transfusion, administration of ALS or cyclosporin-A, or the use of posttransplant injection with a T suppressor activating factor (SAF) [20].

Physical interactions of Igfals

  • The activation of the mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to this sequence [12].

Other interactions of Igfals

  • Consequently, Peg-induced GH deficiency in WT mice severely reduced ALS, IGF-I, and IGFBP-3 in the circulation and caused a severe growth deficit [21].
  • Herein, we show that NADPH oxidase, the main reactive oxygen species-producing enzyme during inflammation, is activated in spinal cords of ALS patients and in spinal cords in a genetic animal model of this disease [16].
  • This growth depression is associated with large decreases in the plasma concentrations of both IGF-I and IGFBP-3, indicating the critical role of ALS in the regulation of circulating levels of these proteins [12].
  • The present study provides the first evidence that IGF-I receptor immunoreactivity was increased in reactive astrocytes in the central nervous system of SOD(G93A) transgenic mice, suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS [22].
  • In addition, reduced hepatic mRNA levels of ALS and GHR in B6 suggests hepatic GH resistance in B6 [23].

Analytical, diagnostic and therapeutic context of Igfals

  • Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans [17].
  • METHODS: To generate an alsin loss-of-function model in an ALS-relevant cell type, we developed a new small interfering RNA electroporation technique that allows efficient knock down of alsin in embryonic rat spinal motoneurons [24].
  • Specific unresponsiveness to skin allografts can be induced in ALS-treated mice by the injection of bone marrow from the graft-donor strain [25].
  • Immune deficiency, however, resulting from neonatal thymectomy or long term ALS administration led A/J animals to remain susceptible when tested at adult age [26].
  • Lymphoid cells were isolated from mouse mammary tumors by isokinetic gradient centrifugation. theta-bearing and ALS-sensitive cells were always the largest subpopulations found in these tumors [27].


  1. 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. Ueki, I., Ooi, G.T., Tremblay, M.L., Hurst, K.R., Bach, L.A., Boisclair, Y.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells. Ooi, G.T., Hurst, K.R., Poy, M.N., Rechler, M.M., Boisclair, Y.R. Mol. Endocrinol. (1998) [Pubmed]
  3. Selective developmental regulation of gene expression for insulin-like growth factor-binding proteins in mouse spinal cord. Arnold, P.M., Ma, J.Y., Citron, B.A., Zoubine, M.N., Festoff, B.W. Spine. (2000) [Pubmed]
  4. The growth hormone-insulin like growth factor axis revisited: lessons from IGF-1 and IGF-1 receptor gene targeting. Yakar, S., Kim, H., Zhao, H., Toyoshima, Y., Pennisi, P., Gavrilova, O., Leroith, D. Pediatr. Nephrol. (2005) [Pubmed]
  5. Oxidative stress mediates impairment of muscle function in transgenic mice with elevated level of wild-type Cu/Zn superoxide dismutase. Peled-Kamar, M., Lotem, J., Wirguin, I., Weiner, L., Hermalin, A., Groner, Y. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Use of neurite outgrowth as an in vitro method of assessing neurotoxicity. Abdulla, E.M., Campbell, I.C. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  7. Lack of apoptosis in mice with ALS. Migheli, A., Atzori, C., Piva, R., Tortarolo, M., Girelli, M., Schiffer, D., Bendotti, C. Nat. Med. (1999) [Pubmed]
  8. Circulating levels of IGF-1 directly regulate bone growth and density. Yakar, S., Rosen, C.J., Beamer, W.G., Ackert-Bicknell, C.L., Wu, Y., Liu, J.L., Ooi, G.T., Setser, J., Frystyk, J., Boisclair, Y.R., LeRoith, D. J. Clin. Invest. (2002) [Pubmed]
  9. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Raoul, C., Estévez, A.G., Nishimune, H., Cleveland, D.W., deLapeyrière, O., Henderson, C.E., Haase, G., Pettmann, B. Neuron (2002) [Pubmed]
  10. Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Mathews, C.E., Leiter, E.H. Diabetes (1999) [Pubmed]
  11. Chronic low-Ca/Mg high-Al diet induces neuronal loss. Kihira, T., Yoshida, S., Yase, Y., Ono, S., Kondo, T. Neuropathology : official journal of the Japanese Society of Neuropathology. (2002) [Pubmed]
  12. Regulation and role of the acid-labile subunit of the 150-kilodalton insulin-like growth factor complex in the mouse. Boisclair, Y.R., Hurst, K.R., Ueki, I., Tremblay, M.L., Ooi, G.T. Pediatr. Nephrol. (2000) [Pubmed]
  13. Organization and chromosomal localization of the gene encoding the mouse acid labile subunit of the insulin-like growth factor binding complex. Boisclair, Y.R., Seto, D., Hsieh, S., Hurst, K.R., Ooi, G.T. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  14. Synthesis of insulinlike growth factor binding proteins and of the acid-labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: regulation by insulin, insulinlike growth factor, and growth hormone. Scharf, J., Ramadori, G., Braulke, T., Hartmann, H. Hepatology (1996) [Pubmed]
  15. Random monoallelic expression of three genes clustered within 60 kb of mouse t complex genomic DNA. Sano, Y., Shimada, T., Nakashima, H., Nicholson, R.H., Eliason, J.F., Kocarek, T.A., Ko, M.S. Genome Res. (2001) [Pubmed]
  16. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Wu, D.C., Ré, D.B., Nagai, M., Ischiropoulos, H., Przedborski, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans. Stadler, S., Wu, Z., Dressendörfer, R.A., Morrison, K.M., Khare, A., Lee, P.D., Strasburger, C.J. J. Immunol. Methods (2001) [Pubmed]
  18. Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis? Almer, G., Kikuchi, H., Teismann, P., Przedborski, S. Ann. Neurol. (2006) [Pubmed]
  19. Hapten-specific IgE antibody responses in mice. VII. Conversion of IgE "non-responder" strains to IgE "responders" by elimination of suppressor T cell activity. Chiorazzi, N., Fox, D.A., Katz, D.H. J. Immunol. (1977) [Pubmed]
  20. T cell-derived factor alone or in combination with immunosuppressive drugs augments prolongation of allogeneic skin graft survival in mice receiving donor-specific transfusion. Gorczynski, R.M., Boulanger, M., Lau, C. J. Immunol. (1987) [Pubmed]
  21. Liver-specific overexpression of the insulin-like growth factor-I enhances somatic growth and partially prevents the effects of growth hormone deficiency. Liao, L., Dearth, R.K., Zhou, S., Britton, O.L., Lee, A.V., Xu, J. Endocrinology (2006) [Pubmed]
  22. Immunohistochemical study on the distribution of insulin-like growth factor I (IGF-I) receptor in the central nervous system of SOD1(G93A) mutant transgenic mice. Chung, Y.H., Joo, K.M., Shin, C.M., Lee, Y.J., Shin, D.H., Lee, K.H., Cha, C.I. Brain Res. (2003) [Pubmed]
  23. Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels. Iida, K., Rosen, C.J., Ackert-Bicknell, C., Thorner, M.O. J. Endocrinol. (2005) [Pubmed]
  24. Alsin/Rac1 signaling controls survival and growth of spinal motoneurons. Jacquier, A., Buhler, E., Schäfer, M.K., Bohl, D., Blanchard, S., Beclin, C., Haase, G. Ann. Neurol. (2006) [Pubmed]
  25. The effect of cyclophosphamide on the splecific unresponsiveness to skin allografts induced in ALS-treated mice infused with donor bone marrow. Wood, M.L., Monaco, A.P. J. Immunol. (1977) [Pubmed]
  26. Neonatal susceptibility to MHV3 infection in mice. I. Transfer of resistance. Levy-Leblond, E., Dupuy, J.M. J. Immunol. (1977) [Pubmed]
  27. In situ lymphoid cells of mouse mammary tumors. II. The characterization of lymphoid cells separated from mouse mammary tumors. Blazer, B.A., Heppner, G.H. J. Immunol. (1978) [Pubmed]
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