Abstract
In an attempt to immortalize the gene products of single neurons, somatic cell hybrids were produced by fusion of embryonic rat dorsal root ganglion (DRG) neurons with mouse neuroblastoma cells. Embryonic day 13 rat DRGs were fused with mouse neuroblastoma cells deficient in hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8). The hybrid cells were selected in medium with 100 microM hypoxanthine/1 microM aminopterin/12 microM thymidine to eliminate the neuroblastoma cells and with cis-hydroxyproline to retard fibroblast growth. Of the 17 lines derived, 4 manifested neuronal properties and were cloned. These lines retain both rat and mouse chromosomes and synthesize characteristic rat and mouse isoenzymes. Neuronal gangliosides, action potentials, and extensive neurite-like processes are exhibited by these hybrid cells, properties characteristic of DRG neurons but not of the neuroblastoma parent. Each line manifests a unique combination of action-potential properties and cell-surface markers, suggesting the selective expression of subsets of DRG neuronal genes. All of these neuronal properties are expressed constitutively, without the need for chemical induction or mitotic inhibition, and stably, without diminution after at least 5 months in culture. These lines may prove useful in the identification and isolation of gene products that characterize individual or small subsets of DRG neurons.
MeSH Terms
Animals
Cell Fusion
Cell Line
Ganglia, Spinal/cytology
Gangliosides/analysis
Hybrid Cells/cytology
Isoenzymes/analysis
Karyotyping
Membrane Potentials
Mice
Neuroblastoma/pathology
Neurons/cytology,physiology
Rats
Chemicals
Gangliosides
Isoenzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Platika D
Boulos M H
Baizer L
Fishman M C
References (24)
24 references, click to expand
-
Establishment of functional clonal lines of neurons from mouse neuroblastoma.
Proc Natl Acad Sci U S A. 1969 Sep;64(1):311-5
PMID: 5263016
-
Cell recognition during neuronal development.
Science. 1984 Sep 21;225(4668):1271-9
PMID: 6474176
-
Development of rat dorsal root ganglion neurones. Studies of cell birthdays and changes in mean cell diameter.
Cell Tissue Res. 1974;153(3):399-413
PMID: 4458950
-
Expression of phenotypes in hybrid somatic cells derived from the nervous system.
Genetics. 1975 Jun;79 Suppl:373-83
PMID: 1150088
-
Continuous cultures of fused cells secreting antibody of predefined specificity.
Nature. 1975 Aug 7;256(5517):495-7
PMID: 1172191
-
Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells.
Proc Natl Acad Sci U S A. 1975 Dec;72(12):4923-7
PMID: 1745
-
Fluorescence analysis of late DNA replication in mouse metaphase chromosomes using BUdR and 33258 Hoechst.
Exp Cell Res. 1976 May;99(2):438-44
PMID: 57878
-
Immunohistochemical evidence for separate populations of somatostatin-containing and substance P-containing primary afferent neurons in the rat.
Neuroscience. 1976;1(2):131-6
PMID: 1004708
-
Proline analogue removes fibroblasts from cultured mixed cell populations.
Nature. 1977 Mar 3;266(5597):63-4
PMID: 758007
-
Phenotypic exclusion in mouse melanoma-rat hepatoma hybrid cells: pigment and albumin production are not reexpressed simultaneously.
Cell. 1978 Nov;15(3):843-54
PMID: 31979
-
Genetics of cultured mammalian cells, as studied by somatic cell hybridization.
Natl Cancer Inst Monogr. 1978 May;(48):21-30
PMID: 372815
-
Monoclonal antibody to a plasma membrane antigen of neurons.
Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913-7
PMID: 388422
-
Control of serum protein production in hepatocyte hybridomas: immortalization and expression of normal hepatocyte genes.
Proc Natl Acad Sci U S A. 1980 Nov;77(11):6616-20
PMID: 6161368
-
Immunofluorescence analysis of the time-course of extinction, reexpression, and activation of albumin production in rat hepatoma-mouse fibroblast heterokaryons and hybrids.
J Cell Biol. 1981 Aug;90(2):339-50
PMID: 7026571
-
Potassium current suppression by quinidine reveals additional calcium currents in neuroblastoma cells.
Proc Natl Acad Sci U S A. 1981 Aug;78(8):5245-9
PMID: 6272298
-
Calcium- and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture.
J Neurophysiol. 1982 Apr;47(4):641-55
PMID: 7069458
-
Permanent cell line expressing human factor VIII-related antigen established by hybridization.
Proc Natl Acad Sci U S A. 1983 Jun;80(12):3734-7
PMID: 6407019
-
Axonal proteins of presynaptic neurons during synaptogenesis.
Science. 1983 Sep 23;221(4617):1294-7
PMID: 6612344
-
Characterization of monoclonal antibody 3G5 and utilization of this antibody to immobilize pancreatic islet cell gangliosides in a solid phase radioassay.
Endocrinology. 1984 Apr;114(4):1338-43
PMID: 6368201
-
Cellular localization and function of the proteins encoded by brain-specific mRNAs.
Cold Spring Harb Symp Quant Biol. 1983;48 Pt 2:477-84
PMID: 6586369
-
Gene expression and the diversity of identified neurons.
Cold Spring Harb Symp Quant Biol. 1983;48 Pt 2:485-92
PMID: 6327171
-
Factors that determine connectivity in the nervous system of Caenorhabditis elegans.
Cold Spring Harb Symp Quant Biol. 1983;48 Pt 2:633-40
PMID: 6586380
-
A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells.
Cell. 1984 Sep;38(2):523-34
PMID: 6147198
-
Microfluorometric detection of deoxyribonucleic acid replication in human metaphase chromosomes.
Proc Natl Acad Sci U S A. 1973 Dec;70(12):3395-9
PMID: 4128545