Cold Spring Harbor Laboratory

About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.

Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression.

Abstract: Expression of hormones in endocrine tumors and derived cell lines of transgenic mice carrying insulin-promoted oncogenes has been investigated by histochemical, immunohistochemical, ultrastructural, and radioimmunologic means Tumors of the pancreas, small intestine, mesentery, and liver were examined Insulin-immunoreactive cells were prevalent in pancreatic tumors, with a significant subpopulation of pancreatic polypeptide-immunoreactive elements Conventional ultrastructural and immunogold analysis identified insulin-storing beta granules in pancreatic tumor cells In contrast, the largest immunoreactive subpopulation of intestinal tumors expressed secretin (53% of total cells), followed by proglucagon-related peptides (15%), glucose-dependent insulinotropic polypeptide (7%), gastrin (7%), pancreatic polypeptide (2%), neurotensin (2%), and somatostatin (1%) No detectable immunoreactivity for either insulin or serotonin was observed Electron microscopy and immunogold labeling showed that intestinal tumor cells contained secretin-storing S-type granules Lymph node and liver tumors contained secretin-immunoreactive cells with ultrastructural features similar to those of intestinal tumors In addition, high levels of circulating insulinlike and secretinlike immunoreactants were detectable Analogous hormone profiles were identified in tumor cell lines and culture media Large T-antigen immunoreactivity was detected in all the nuclei of neoplastic cells, as well as in insulin-immunoreactive elements of non-neoplastic islets and pancreatic ducts and in some secretin-immunoreactive cells of small intestinal mucosa These data indicate that neuroendocrine tumors arise both in beta cell and S-cell subpopulations of transgenic mice

Atrial natriuretic factor-SV40 T antigen transgenes produce tumors and cardiac arrhythmias in mice

Abstract: Transgenic mice that carry fusions between the transcriptional regulatory sequences of atrial natriuretic factor (a hormone intimately involved in the regulation of blood pressure) and those encoding SV40 T antigen (an oncoprotein) were generated. Although both atria express the fusion gene, the pathological response to T antigen is asymmetrical. The right atrium undergoes a several hundredfold increase in mass while the left atrium remains relatively normal in size. Hyperplasia is accompanied by a progressive increase in both the frequency and severity of abnormalities in the atrial conduction system, which ultimately result in death.

p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation.

Abstract: Heterozygous germline mutations in p63 , a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth In mice lacking p63 , all ectodermal organs fail to develop, and stratification of the epidermis is absent We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63 -deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally The N-terminally truncated isoform of p63 (ΔNp63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal stratification Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed withΔ Np63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants In addition, β-catenin and Edar transcripts were significantly reduced in skin ectoderm We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways