Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Nov 1;90(21):10360–10364. doi: 10.1073/pnas.90.21.10360

Cloning of cDNA for the alpha subunit of mouse insulin-like growth factor I receptor and the role of the receptor in metanephric development.

J Wada 1, Z Z Liu 1, K Alvares 1, A Kumar 1, E Wallner 1, H Makino 1, Y S Kanwar 1
PMCID: PMC47774  PMID: 8234298

Abstract

Various growth factors influence mammalian development by binding to specific cell surface receptors. These interactions are followed by a series of intracellular transductional events leading to a wide variety of biological effects. To establish the role of insulin-like growth factor I receptor (IGF-IR) in renal development, cDNA for the alpha subunit of the mouse IGF-IR was isolated, characterized, and used in expression studies and antisense experiments in a metanephric organ culture system. A 989-bp insert, encoding the signal peptide and 299 amino acids, isolated from a newborn mouse kidney cDNA library had 99% and 91% homology with the nucleotide sequences encoding the rat and the human IGF-IR, respectively. An approximately 11-kb message was readily detected by Northern blot analysis of RNA from the developing kidney at day 13 of gestation, and it declined during the subsequent embryonal and neonatal periods. In situ hybridization revealed high levels of message over the ureteric bud and its branches. A lower level of message was seen in the neonatal kidney, confined mainly to the tubules. Antisense oligodeoxynucleotide-treated metanephric kidneys were reduced in size and had a decreased population of nephrons with marked disorganization of ureteric bud branches. Immunofluorescence studies indicated an arrest of IGF-IR translation after antisense exposure. Immunoprecipitation studies showed a marked decrease in the biosynthesis of various extracellular matrix proteins that serve as regulators of morphogenesis. These studies suggest that the nucleotide sequence encoding the alpha subunit of mouse IGF-IR is highly conserved and that the receptor might play an essential role in the organogenesis of the kidney.

Full text

PDF
10361

Images in this article

10361Fig. 1
on p.10361
10362Fig. 3
on p.10362
10362Fig. 4
on p.10362
10363Fig. 5
on p.10363
10363Fig. 6
on p.10363
10363Fig. 7
on p.10363

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahamson D. R. Glomerulogenesis in the developing kidney. Semin Nephrol. 1991 Jul;11(4):375–389. [PubMed] [Google Scholar]
  2. Avner E. D., Ellis D., Temple T., Jaffe R. Metanephric development in serum-free organ culture. In Vitro. 1982 Aug;18(8):675–682. doi: 10.1007/BF02796422. [DOI] [PubMed] [Google Scholar]
  3. Banerjee S. D., Cohn R. H., Bernfield M. R. Basal lamina of embryonic salivary epithelia. Production by the epithelium and role in maintaining lobular morphology. J Cell Biol. 1977 May;73(2):445–463. doi: 10.1083/jcb.73.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernfield M., Kokenyesi R., Kato M., Hinkes M. T., Spring J., Gallo R. L., Lose E. J. Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol. 1992;8:365–393. doi: 10.1146/annurev.cb.08.110192.002053. [DOI] [PubMed] [Google Scholar]
  5. Bernstein J., Cheng F., Roszka J. Glomerular differentiation in metanephric culture. Lab Invest. 1981 Aug;45(2):183–190. [PubMed] [Google Scholar]
  6. Cazenave C., Stein C. A., Loreau N., Thuong N. T., Neckers L. M., Subasinghe C., Hélène C., Cohen J. S., Toulmé J. J. Comparative inhibition of rabbit globin mRNA translation by modified antisense oligodeoxynucleotides. Nucleic Acids Res. 1989 Jun 12;17(11):4255–4273. doi: 10.1093/nar/17.11.4255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Drummond I. A., Madden S. L., Rohwer-Nutter P., Bell G. I., Sukhatme V. P., Rauscher F. J., 3rd Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science. 1992 Jul 31;257(5070):674–678. doi: 10.1126/science.1323141. [DOI] [PubMed] [Google Scholar]
  9. Lelongt B., Makino H., Dalecki T. M., Kanwar Y. S. Role of proteoglycans in renal development. Dev Biol. 1988 Aug;128(2):256–276. doi: 10.1016/0012-1606(88)90289-8. [DOI] [PubMed] [Google Scholar]
  10. Liu Z. Z., Carone F. A., Dalecki T. M., Lelongt B., Wallner E. I., Kanwar Y. S. Mannose-induced dysmorphogenesis of metanephric kidney. Role of proteoglycans and adenosine triphosphate. J Clin Invest. 1992 Oct;90(4):1205–1218. doi: 10.1172/JCI115982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rogers S. A., Ryan G., Hammerman M. R. Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro. J Cell Biol. 1991 Jun;113(6):1447–1453. doi: 10.1083/jcb.113.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith C. I., Hilfer S. R., Searls R. L., Nathanson M. A., Allodoli M. D. Effects of beta-D-xyloside on differentiation of the respiratory epithelium in the fetal mouse lung. Dev Biol. 1990 Mar;138(1):42–52. doi: 10.1016/0012-1606(90)90175-i. [DOI] [PubMed] [Google Scholar]
  15. Solursh M., Reiter R. S., Jensen K. L., Kato M., Bernfield M. Transient expression of a cell surface heparan sulfate proteoglycan (syndecan) during limb development. Dev Biol. 1990 Jul;140(1):83–92. doi: 10.1016/0012-1606(90)90055-n. [DOI] [PubMed] [Google Scholar]
  16. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  17. Ullrich A., Gray A., Tam A. W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Le Bon T., Kathuria S., Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. doi: 10.1002/j.1460-2075.1986.tb04528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Werner H., Woloschak M., Adamo M., Shen-Orr Z., Roberts C. T., Jr, LeRoith D. Developmental regulation of the rat insulin-like growth factor I receptor gene. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7451–7455. doi: 10.1073/pnas.86.19.7451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yip C. C., Hsu H., Patel R. G., Hawley D. M., Maddux B. A., Goldfine I. D. Localization of the insulin-binding site to the cysteine-rich region of the insulin receptor alpha-subunit. Biochem Biophys Res Commun. 1988 Nov 30;157(1):321–329. doi: 10.1016/s0006-291x(88)80050-0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES