Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Jan 11;19(1):169–177. doi: 10.1093/nar/19.1.169

Molecular cloning of the mouse CCK gene: expression in different brain regions and during cortical development.

M Vitale 1, A Vashishtha 1, E Linzer 1, D J Powell 1, J M Friedman 1
PMCID: PMC333548  PMID: 2011497

Abstract

In this paper we describe experiments that address specific issues concerning the regulation of the mouse cholecystokinin gene in brain and intestine. The mouse cholecystokinin gene was cloned and sequenced. Extensive homology among the mouse, man and rat genes was noted particularly in the three exons and the regions upstream of the RNA start site. RNAse protection assays for each of the three exons were used to demonstrate that CCK is expressed in only a subset of tissues and that the same cap site and splice choices are used in brain, intestine as well as in cerebellum, cortex, midbrain, hypothalamus and hippocampus. CCK RNA was also noted to be detectable in kidney. Thus the same gene using the same promoter is expressed in subsets of cells that differ in their biochemical, morphologic and functional characteristics. The level of expression of CCK was also monitored during mouse cortical development and the appearance of CCK RNA was compared to glutamate decarboxylase (GAD), enkephalin and somatostatin. It was noted that each of these cortical markers was first expressed at different times during cortical development. The appearance of CCK RNA during intestinal development was also measured and found to precede appearance in cortex by several days.

Full text

PDF
169

Images in this article

Selected References

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

  1. Bayon A., Shoemaker W. J., Bloom F. E., Mauss A., Guillemin R. Perinatal development of the endorphin- and enkephalin-containing systems in the rat brain. Brain Res. 1979 Dec 21;179(1):93–101. doi: 10.1016/0006-8993(79)90493-1. [DOI] [PubMed] [Google Scholar]
  2. Bond R. W., Jansen K. R., Gottlieb D. I. Pattern of expression of glutamic acid decarboxylase mRNA in the developing rat brain. Proc Natl Acad Sci U S A. 1988 May;85(9):3231–3234. doi: 10.1073/pnas.85.9.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Branks P. L., Wilson M. C. Patterns of gene expression in the murine brain revealed by in situ hybridization of brain-specific mRNAs. Brain Res. 1986 Jul;387(1):1–16. doi: 10.1016/0169-328x(86)90015-x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Clayton D. F., Huecas M. E., Sinclair-Thompson E. Y., Nastiuk K. L., Nottebohm F. Probes for rare mRNAs reveal distributed cell subsets in canary brain. Neuron. 1988 May;1(3):249–261. doi: 10.1016/0896-6273(88)90146-8. [DOI] [PubMed] [Google Scholar]
  6. Costa R. H., Lai E., Darnell J. E., Jr Transcriptional control of the mouse prealbumin (transthyretin) gene: both promoter sequences and a distinct enhancer are cell specific. Mol Cell Biol. 1986 Dec;6(12):4697–4708. doi: 10.1128/mcb.6.12.4697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  8. Deschenes R. J., Haun R. S., Funckes C. L., Dixon J. E. A gene encoding rat cholecystokinin. Isolation, nucleotide sequence, and promoter activity. J Biol Chem. 1985 Jan 25;260(2):1280–1286. [PubMed] [Google Scholar]
  9. Deschenes R. J., Lorenz L. J., Haun R. S., Roos B. A., Collier K. J., Dixon J. E. Cloning and sequence analysis of a cDNA encoding rat preprocholecystokinin. Proc Natl Acad Sci U S A. 1984 Feb;81(3):726–730. doi: 10.1073/pnas.81.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Enoch T., Zinn K., Maniatis T. Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Friedman J. M., Babiss L. E., Clayton D. F., Darnell J. E., Jr Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression. Mol Cell Biol. 1986 Nov;6(11):3791–3797. doi: 10.1128/mcb.6.11.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friedman J., Schneider B. S., Powell D. Differential expression of the mouse cholecystokinin gene during brain and gut development. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5593–5597. doi: 10.1073/pnas.82.17.5593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Glowinski J., Iversen L. L. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem. 1966 Aug;13(8):655–669. doi: 10.1111/j.1471-4159.1966.tb09873.x. [DOI] [PubMed] [Google Scholar]
  14. Goldman S. A., Monahan J. W., Schneider B. S. The regional and subcellular development of cholecystokinin immunoreactivity in vertebrate brain. Brain Res. 1985 Oct;354(2):237–246. doi: 10.1016/0165-3806(85)90175-0. [DOI] [PubMed] [Google Scholar]
  15. Gubler U., Chua A. O., Young D., Fan Z. W., Eng J. Cholecystokinin mRNA in porcine cerebellum. J Biol Chem. 1987 Nov 5;262(31):15242–15245. [PubMed] [Google Scholar]
  16. Hendry S. H., Jones E. G., DeFelipe J., Schmechel D., Brandon C., Emson P. C. Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6526–6530. doi: 10.1073/pnas.81.20.6526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hiromi Y., Gehring W. J. Regulation and function of the Drosophila segmentation gene fushi tarazu. Cell. 1987 Sep 11;50(6):963–974. doi: 10.1016/0092-8674(87)90523-x. [DOI] [PubMed] [Google Scholar]
  18. Hökfelt T., Skirboll L., Rehfeld J. F., Goldstein M., Markey K., Dann O. A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin-like peptide: evidence from immunohistochemistry combined with retrograde tracing. Neuroscience. 1980;5(12):2093–2124. doi: 10.1016/0306-4522(80)90127-x. [DOI] [PubMed] [Google Scholar]
  19. Innis R. B., Corrêa F. M., Uhl G. R., Schneider B., Snyder S. H. Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain. Proc Natl Acad Sci U S A. 1979 Jan;76(1):521–525. doi: 10.1073/pnas.76.1.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kaufman D. L., McGinnis J. F., Krieger N. R., Tobin A. J. Brain glutamate decarboxylase cloned in lambda gt-11: fusion protein produces gamma-aminobutyric acid. Science. 1986 May 30;232(4754):1138–1140. doi: 10.1126/science.3518061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McGregor G. P., Woodhams P. L., O'Shaughnessy D. J., Ghatei M. A., Polak J. M., Bloom S. R. Developmental changes in bombesin, substance P, somatostatin and vasoactive intestinal polypeptide in the rat brain. Neurosci Lett. 1982 Jan 22;28(1):21–27. doi: 10.1016/0304-3940(82)90202-6. [DOI] [PubMed] [Google Scholar]
  22. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mezey E., Reisine T. D., Skirboll L., Beinfeld M., Kiss J. Z. Role of cholecystokinin in corticotropin release: coexistence with vasopressin and corticotropin-releasing factor in cells of the rat hypothalamic paraventricular nucleus. Proc Natl Acad Sci U S A. 1986 May;83(10):3510–3512. doi: 10.1073/pnas.83.10.3510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miller F. D., Naus C. C., Higgins G. A., Bloom F. E., Milner R. J. Developmentally regulated rat brain mRNAs: molecular and anatomical characterization. J Neurosci. 1987 Aug;7(8):2433–2444. [PMC free article] [PubMed] [Google Scholar]
  25. Montminy M. R., Low M. J., Tapia-Arancibia L., Reichlin S., Mandel G., Goodman R. H. Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells. J Neurosci. 1986 Apr;6(4):1171–1176. doi: 10.1523/JNEUROSCI.06-04-01171.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Powell D. J., Friedman J. M., Oulette A. J., Krauter K. S., Darnell J. E., Jr Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver. J Mol Biol. 1984 Oct 15;179(1):21–35. doi: 10.1016/0022-2836(84)90304-8. [DOI] [PubMed] [Google Scholar]
  29. ROBERTS E., HARMAN P. J., FRANKEL S. gamma Aminobutyric acid content and glutamic decarboxylase activity in developing mouse brain. Proc Soc Exp Biol Med. 1951 Dec;78(3):799–803. doi: 10.3181/00379727-78-19224. [DOI] [PubMed] [Google Scholar]
  30. Rehfeld J. F. Immunochemical studies on cholecystokinin. II. Distribution and molecular heterogeneity in the central nervous system and small intestine of man and hog. J Biol Chem. 1978 Jun 10;253(11):4022–4030. [PubMed] [Google Scholar]
  31. 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]
  32. Schneider B. S., Helson L., Monahan J. W., Friedman J. M. Expression of the cholecystokinin gene by cultured human primitive neuroepithelioma cell lines. J Clin Endocrinol Metab. 1989 Aug;69(2):411–419. doi: 10.1210/jcem-69-2-411. [DOI] [PubMed] [Google Scholar]
  33. Schneider B. S., Monahan J. W., Hirsch J. Brain cholecystokinin and nutritional status in rats and mice. J Clin Invest. 1979 Nov;64(5):1348–1356. doi: 10.1172/JCI109591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Scholnick S. B., Bray S. J., Morgan B. A., McCormick C. A., Hirsh J. CNS and hypoderm regulatory elements of the Drosophila melanogaster dopa decarboxylase gene. Science. 1986 Nov 21;234(4779):998–1002. doi: 10.1126/science.3095924. [DOI] [PubMed] [Google Scholar]
  35. Schwartz J. P., Simantov R. Developmental expression of proenkephalin mRNA in rat striatum and in striatal cultures. Brain Res. 1988 May 16;468(2):311–314. doi: 10.1016/0165-3806(88)90144-7. [DOI] [PubMed] [Google Scholar]
  36. Shiosaka S., Takatsuki K., Sakanaka M., Inagaki S., Takagi H., Senba E., Kawai Y., Iida H., Minagawa H., Hara Y. Ontogeny of somatostatin-containing neuron system of the rat: immunohistochemical analysis. II. Forebrain and diencephalon. J Comp Neurol. 1982 Jan 20;204(3):211–224. doi: 10.1002/cne.902040302. [DOI] [PubMed] [Google Scholar]
  37. Sims K. L., Pitts F. N., Jr Brain glutamate decarboxylase: changes in the developing rat brain. J Neurochem. 1970 Nov;17(11):1607–1612. doi: 10.1111/j.1471-4159.1970.tb03731.x. [DOI] [PubMed] [Google Scholar]
  38. Somogyi P., Hodgson A. J., Smith A. D., Nunzi M. G., Gorio A., Wu J. Y. Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material. J Neurosci. 1984 Oct;4(10):2590–2603. doi: 10.1523/JNEUROSCI.04-10-02590.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Takahashi Y., Fukushige S., Murotsu T., Matsubara K. Structure of human cholecystokinin gene and its chromosomal location. Gene. 1986;50(1-3):353–360. doi: 10.1016/0378-1119(86)90339-2. [DOI] [PubMed] [Google Scholar]
  40. Terao M., Watanabe Y., Mishina M., Numa S. Sequence requirement for transcription in vivo of the human preproenkephalin A gene. EMBO J. 1983;2(12):2223–2228. doi: 10.1002/j.1460-2075.1983.tb01727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Voigt M. M., Uhl G. R. Preprocholecystokinin mRNA in rat brain: regional expression includes thalamus. Brain Res. 1988 Nov;464(3):247–253. doi: 10.1016/0169-328x(88)90031-9. [DOI] [PubMed] [Google Scholar]
  42. Yoshikawa K., Williams C., Sabol S. L. Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and distribution in the central nervous system. J Biol Chem. 1984 Nov 25;259(22):14301–14308. [PubMed] [Google Scholar]
  43. Zingg H. H., Goodman R. H., Habener J. F. Developmental expression of the rat somatostatin gene. Endocrinology. 1984 Jul;115(1):90–94. doi: 10.1210/endo-115-1-90. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES