Transgenic Mouse Model: a New Approach for the Investigation of Endocrine Pancreatic B-cell Growth

Overview

Journal Gut

Specialty Gastroenterology

Date 1987 Jan 1

PMID 2826309

Citations 6

Authors

R F Power

R Holm

A E Bishop

I M Varndell

S Alpert

D Hanahan

J M Polak

Affiliations

Soon will be listed here.

Abstract

The transformation and adaptation of pancreatic insulin-producing (B) cells has been studied in a transgenic mouse model using a panel of antisera recognising peptides and general neuroendocrine markers at both light and electron microscopical levels. Stages of tumour genesis in the transgenic mouse model from hyperplasia to neoplasia, have been compared with human B-cell tumours. A normal complement of peptide containing cells was seen in the transgenic mouse pancreas, but cells containing pro-insulin-derived peptides became more numerous as hyperplasia commenced. The transgenic mouse tumours were composed of B cells, although 30-35% of the tumours were also found to contain PP cells--a finding which is directly comparable with that in human insulin-producing tumours. NSE, 7B2 and chromogranin immunoreactivities were found in most cells from all the tumours examined. Antisera to PGP 9.5, a novel marker for elements of the neuroendocrine system, were found to stain hyperplastic and neoplastic B-cells intensely. In contrast, normal mouse B-cells did not show PGP 9.5 immunoreactivity thus it appears that PGP 9.5 is differentially expressed in transformed and/or growing mouse B-cells and hence may be used as an indicator in studies of early tumour growth.

Citing Articles

Gut endocrine and neural peptides.

Bishop A, Polak J Endocr Pathol. 2020; 1(1):4-24.

PMID: 32138398 DOI: 10.1007/BF02915151.

Insulinomas derived from hyperplastic intra-hepatic islet transplants.

Dombrowski F, Klingmuller D, Pfeifer U Am J Pathol. 1998; 152(4):1025-38.

PMID: 9546363 PMC: 1858236.

Endocrine pancreatic tumors in MSV-SV40 large T transgenic mice.

Gotz W, Schucht C, Roth J, Theuring F, Herken R Am J Pathol. 1993; 142(5):1493-503.

PMID: 8388173 PMC: 1886916.

Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.

Efrat S, Linde S, Kofod H, Spector D, Delannoy M, Grant S Proc Natl Acad Sci U S A. 1988; 85(23):9037-41.

PMID: 2848253 PMC: 282658. DOI: 10.1073/pnas.85.23.9037.

A morphological analysis endocrine tumour genesis in pancreas and anterior pituitary of AVP/SV40 transgenic mice.

Rindi G, Bishop A, Murphy D, Solcia E, Hogan B, Polak J Virchows Arch A Pathol Anat Histopathol. 1988; 412(3):255-66.

PMID: 2829418 DOI: 10.1007/BF00737150.

References

Doran J, Jackson P, Kynoch P, Thompson R . Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem. 1983; 40(6):1542-7. DOI: 10.1111/j.1471-4159.1983.tb08124.x. View

Gulbenkian S, Wharton J, Polak J . The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). J Auton Nerv Syst. 1987; 18(3):235-47. DOI: 10.1016/0165-1838(87)90122-6. View

Smith A, Winkler H . A simple method for the isolation of adrenal chromaffin granules on a large scale. Biochem J. 1967; 103(2):480-2. PMC: 1270431. DOI: 10.1042/bj1030480. View

Kirshner A, Kirshner N . A specific soluble protein from the catecholamine storage vesicles of bovine adrenal medulla. II. Physical characterization. Biochim Biophys Acta. 1969; 181(1):219-25. DOI: 10.1016/0005-2795(69)90244-x. View

Grimelius L . The argyrophil reaction in islet cells of adult human pancreas studies with a new silver nitrate procedure. Acta Soc Med Ups. 1968; 73(5-6):271-94. View

Polak J, Bloom S, Adrian T, Heitz P, Bryant M, Pearse A . Pancreatic polypeptide in insulinomas, gastrinomas, vipomas, and glucagonomas. Lancet. 1976; 1(7955):328-30. DOI: 10.1016/s0140-6736(76)90084-2. View

Marangos P, Zomzely-Neurath C, YORK C . Determination and characterization of neuron specific protein (NSP) associated enolase activity. Biochem Biophys Res Commun. 1976; 68(4):1309-16. DOI: 10.1016/0006-291x(76)90339-9. View

Winkler H . The composition of adrenal chromaffin granules: an assessment of controversial results. Neuroscience. 1976; 1(2):65-80. DOI: 10.1016/0306-4522(76)90001-4. View

Schmechel D, Marangos P, Brightman M . Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978; 276(5690):834-6. DOI: 10.1038/276834a0. View

10.

Cairns J . The origin of human cancers. Nature. 1981; 289(5796):353-7. DOI: 10.1038/289353a0. View

11.

Gordon J, Scangos G, Plotkin D, Barbosa J, Ruddle F . Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A. 1980; 77(12):7380-4. PMC: 350507. DOI: 10.1073/pnas.77.12.7380. View

12.

Heitz P, Kasper M, Polak J, Kloppel G . Pancreatic endocrine tumors. Hum Pathol. 1982; 13(3):263-71. DOI: 10.1016/s0046-8177(82)80183-4. View

13.

Bishop A, Polak J, Facer P, Ferri G, Marangos P, Pearse A . Neuron specific enolase: a common marker for the endocrine cells and innervation of the gut and pancreas. Gastroenterology. 1982; 83(4):902-15. View

14.

Palmiter R, Brinster R, Hammer R, Trumbauer M, Rosenfeld M, Birnberg N . Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature. 1982; 300(5893):611-5. PMC: 4881848. DOI: 10.1038/300611a0. View

15.

Hsi K, Seidah N, De Serres G, Chretien M . Isolation and NH2-terminal sequence of a novel porcine anterior pituitary polypeptide. Homology to proinsulin, secretin and Rous sarcoma virus transforming protein TVFV60. FEBS Lett. 1982; 147(2):261-6. DOI: 10.1016/0014-5793(82)81055-7. View

16.

Bendayan M, ZOLLINGER M . Ultrastructural localization of antigenic sites on osmium-fixed tissues applying the protein A-gold technique. J Histochem Cytochem. 1983; 31(1):101-9. DOI: 10.1177/31.1.6187796. View

17.

Thompson R, Doran J, Jackson P, Dhillon A, Rode J . PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983; 278(1-2):224-8. DOI: 10.1016/0006-8993(83)90241-x. View

18.

Underwood L, DErcole A . Insulin and insulin-like growth factors/somatomedins in fetal and neonatal development. Clin Endocrinol Metab. 1984; 13(1):69-89. DOI: 10.1016/s0300-595x(84)80009-2. View

19.

Hanahan D . Oncogenes in transgenic mice. Nature. 1984; 312(5994):503-4. DOI: 10.1038/312503a0. View

20.

Bradbury J, Thompson R . Immunoassay of the neuronal and neuroendocrine marker PGP 9.5 in human tissues. J Neurochem. 1985; 44(2):651-3. DOI: 10.1111/j.1471-4159.1985.tb05461.x. View