| 1. |
- Gobl, Anders, et al.
(author)
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Assignment of the mouse homologue of a MEN 1 candidate gene, phospholipase C-beta3 (Plcb3), to chromosome region 19B by FISH
- 1995
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In: Cytogenetics and Cell Genetics. - : S. Karger AG. - 0301-0171 .- 1421-9816. ; 71:3, s. 257-259
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Journal article (peer-reviewed)abstract
- A recent study using comparative mapping analysis suggests that the proximal segment of mouse chromosome 19 contains the mouse homologs of the human multiple endocrine neoplasia type 1 (MEN1) flanking markers proximal to the locus. We have recently shown that phospholipase C-beta 3 (PLCB3) is a candidate gene for the MEN1 syndrome. In the present investigation we used fluorescence in situ hybridization with a genomic DNA clone for mouse Plcb3, and mapped the locus to chromosome region 19B. This is in agreement with the comparative mapping of the MEN1 flanking markers in mouse.
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| 2. |
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| 3. |
- Stålberg, Peter, et al.
(author)
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Suppression of the neoplastic phenotype by transfection of phospholipase C3 to neuroendocrine tumor cells
- 1999
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In: FEBS Letters. - 0014-5793 .- 1873-3468. ; 450:3, s. 210-216
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Journal article (peer-reviewed)abstract
- The expression of phospholipase C beta 3 (PLCB3) is low or absent in several neuroendocrine neoplasias. To investigate the role of PLCB3 in the neuroendocrine tumorigenesis, we transfected a PLCB3 construct to three neuroendocrine tumor cell lines with a low PLCB3 expression. The growth rate and tumorigenicity were assessed in vitro by [3H]thymidine incorporation and cell counting, in vivo, by xenografting to nude mice. In vitro, PLCB3 expressing clones showed a significant growth inhibition. The tumor weight was reduced for one of the two xenografted PLCB3-transfected cell lines and in both, a reduced number of proliferating (Ki-67 positive) cells was observed. This study implies an essential role for PLCB3 in the neuroendocrine tumorigenesis.
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| 4. |
- Wang, Shu, et al.
(author)
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Molecular cloning and characterization of a cDNA encoding mouse phospholipase C-β3
- 1998
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In: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1393:1, s. 173-178
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Journal article (other academic/artistic)abstract
- A cDNA encoding mouse PLC-beta3 (mPLC-beta3) was identified by screening a mouse kidney cDNA library and using the rapid amplification of cDNA ends (RACE) method. The predicted open reading frame was 3705 bp in length. The deduced 1235 amino acid (aa) sequence shares 95.3% and 92% homology with the sequences of rat and human PLC-beta3, respectively. The corresponding mRNA is highly expressed in kidney, skeletal muscle, liver, lung, heart and brain. In spleen, mPLC-beta3 mRNA was not detectable, which is in contrast to humans where there is a distinct expression. Using ultrastructural immunocytochemistry, mPLC-beta3 expression was detected in the heterochromatin of the nucleus in mouse brain neurons. The observation of PLC-beta3 nuclear localization suggests that PLC-beta3 may have intranuclear functions.
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| 5. |
- Wang, Shu
(author)
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Targeted disruption and subcellular distribution of phospholipase C 3
- 1999
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Doctoral thesis (other academic/artistic)abstract
- Phosphatidylinositol specific phospholipase C (PLC) isoforms are key enzymes in the signal transduction pathway that control many cellular processes including cell proliferation, hormone secretion and egg fertilization. The PLCβ3 gene, assigned to the multiple endocrine neoplasia type 1 (MEN1) locus, has been implicated in endocrine tumorigenesis due to the low expression in several endocrine tumors. In order to study the biological function of PLCβ3, we have isolated and characterized the mouse cDNA as well as the genomic DNA. We found that the gene encompasses 31 exons, encodes a protein of 1235 amino acids. We have also mapped the gene to mouse chromosome 19B and disrupted the gene. Homozygous inactivation of the gene was lethal at embryonic day 2.5. PLCβ3 deficient embryos, cultured in vitro, showed poor embryonicorganization as well as reduction of cell numbers and failed to form blastocoele cavities. PLCβ3 protein was expressed in unfertilized mouse eggs, 3-cell and egg cylinder stages of wild type embryos as detected by immunohistochemistry. Although expression of the protein in the heterozygous mice was reduced by approximately 50% compared to wild type littermates, they showed no specific phenotype and remained healthy for at least two generations.The subcellular distribution of four different PLC isozymes in rodent pancreas and gastric mucosa was examined by electron microscope immunocytochemistry. PLCβ1 was exclusively expressed in zymogen granules of the pancreatic acinar cells. PLCβ2 and PLCβ3 were located in the endoplasmic reticulum (ER) of acinar and gastric mucosa cells. Furthermore, both PLCβ2 and PLCβ3 were highly expressed in the heterochromatin areas of the gastric mucosa cell nuclei. In neurons of the mouse brain, PLCβ3 exhibited an expression pattern similar to that of the gastric mucosa. PLCβ3 displayed a weak labeling in nuclei and BR of pancreatic endocrine cells. In contrast to PLCβ3, PLCβ2 was present in secretory granules of pancreatic acinar cells and endocrine cells. PLCγ1 was present in the secretory granules of both pancreatic acinar cells and endocrine cells.
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| 6. |
- Wang, Shu, et al.
(author)
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Targeted disruption of the mouse phospholipase C β3 gene results in early embryonic lethality
- 1998
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In: FEBS Letters. - 0014-5793 .- 1873-3468. ; 441:2, s. 261-265
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Journal article (other academic/artistic)abstract
- In order to investigate the biological function of phosphatidylinositol-specific phospholipase C (PLC) we generated mutant mice by gene targeting. Homozygous inactivation of PLCbeta3 is lethal at embryonic day 2.5. These mutants show poor embryonic organization as well as reduced numbers of cells. Identical phenotypes were recorded in homozygous mutants generated from two independently targeted embryonic stem cell clones. Heterozygous mutant mice, however, are viable and fertile for at least two generations. We also showed that mouse PLCbeta3 is expressed in unfertilized eggs, 3-cell and egg cylinder stages of embryos. In conclusion, these results indicate that PLCbeta3 expression is essential for early mouse embryonic development.
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