Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages

1994 ◽  
Vol 266 (6) ◽  
pp. G987-G1003 ◽  
Author(s):  
P. Falk ◽  
K. A. Roth ◽  
J. I. Gordon
Keyword(s):  
Epithelial Cell ◽  
Transgenic Mice ◽  
Intestinal Epithelial Cell ◽  
Cell Lineage ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Intestinal Epithelial ◽  
Cell Lineages ◽  
Carbohydrate Specificities

We have used histochemical methods to survey the cellular patterns of binding of a panel of 45 lectins with well-defined carbohydrate specificities to sections prepared from various regions of the gastric-to-colonic axis of fetal, neonatal, and adult FVB/N mouse gut. The results suggest that lectins can be used as remarkably sensitive tools to describe the differentiation programs of gastric and intestinal epithelial cell lineages as a function of their position along the cephalocaudal axis of the gut and as a function of developmental stage. Studies of intestinal isografts and transgenic mice that express Simian virus-40 T antigen in enterocytes suggest that many of these cell lineage-specific and spatial patterns of glycoconjugate production can be established and maintained in the absence of exposure to luminal contents and in the presence of specific proliferative abnormalities. This lectin panel should be useful for operationally defining subpopulations of the principal gut epithelial cell lineages in normal strains of mice, for describing variations in gut epithelial cell differentiation programs in mutant and transgenic mice, and for recovering specific epithelial cell lineages or subpopulations.

Moluccella laevis lectin, a marker for cellular differentiation programs in mouse gut epithelium

1995 ◽  
Vol 268 (4) ◽  
pp. G553-G567 ◽  
Author(s):  
P. Falk ◽  
R. G. Lorenz ◽  
N. Sharon ◽  
J. I. Gordon
Keyword(s):  
Epithelial Cell ◽  
Program Analysis ◽  
Cell Biology ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Dominant Negative ◽  
Gastric Epithelium ◽  
Cell Hyperplasia ◽  
Cell Lineages

We have assembled a system for testing the hypothesis that changes in glycoconjugate production represent markers for defining developmental, spatial, and environmental influences on the proliferation and differentiation programs of various mouse gut epithelial cell lineages. Multilabel immunohistochemical methods were used to survey the interactions of purified lectins with 1) normal fetal, neonatal, and adult FVB/N mouse gut, 2) gastric and intestinal isografts harvested at various developmental stages, and 3) transgenic mouse models of intestinal epithelial cell hyperplasia, dysplasia, and/or neoplasia. As a demonstration of the system's utility, we used the recently purified, alpha-N-acetyl-D-galactosamine-specific, Moluccella laevis lectin (MLL). In the adult FVB/N mouse stomach, MLL only recognizes glycoconjugates produced by a population of nonproliferating neck and prezymogenic cells that occupy a pivotal point in the complex, migration-associated differentiation program of the zymogenic cell lineage. In the developing FVB/N stomach, MLL binds to members of the zymogenic and pit lineages even before morphogenesis of gastric units is completed. Expression of MLL epitopes in pit cells is restricted to the period before the gastric epithelium has completed its morphoregulatory program. Analysis of gastric isografts indicates that these lineage- and developmental stage-specific patterns of glycoconjugate accumulation are not influenced by normal luminal contents. In the adult FVB/N intestine, MLL binding can be used to operationally define variations in the differentiation programs of 1) members of the enteroendocrine and goblet cell lineages during their migration along the crypt-to-villus axis and 2) cells comprising the follicle-associated epithelium overlying Peyer's patches. Accumulation of MLL epitopes in villus-associated enterocytes does not appear to be affected when these cells are induced to reenter the cell cycle by simian virus 40 large T antigen (SV40 TAg). MLL reactivity is not diminished when enterocytes begin to dedifferentiate as a result of production of SV40 TAg, human K-rasVal12, and a dominant negative human p53 mutant. The lack of change in MLL binding properties may reflect the brief residence time of enterocytes on the villus. These results indicate that glycoconjugate production represents a very useful tool for studying gut epithelial cell biology. Preliminary studies suggest that this is also true in the human gut.

NF-κB blockade exacerbates experimental colitis in transgenic mice expressing an intestinal epithelial cell (IEC) specific IκB super-repressor

2001 ◽  
Vol 120 (5) ◽  
pp. A70 ◽  
Author(s):  
Maria Pia Russo ◽  
Francois Boubreau ◽  
Fengling Li ◽  
Asit Panja ◽  
Peter G. Traber ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Transgenic Mice ◽  
Intestinal Epithelial Cell ◽  
Experimental Colitis ◽  
Intestinal Epithelial

scholarly journals The retinoblastoma protein-binding region of simian virus 40 large T antigen alters cell cycle regulation in lenses of transgenic mice.

1994 ◽  
Vol 14 (10) ◽  
pp. 6743-6754 ◽  
Author(s):  
L Fromm ◽  
W Shawlot ◽  
K Gunning ◽  
J S Butel ◽  
P A Overbeek
Keyword(s):  
Cell Cycle ◽  
Transgenic Mice ◽  
Retinoblastoma Protein ◽  
Simian Virus 40 ◽  
Cell Types ◽  
Simian Virus ◽  
T Antigen ◽  
Lens Fiber ◽  
Large T Antigen ◽  
Fiber Cells

Regulation of the cell cycle is a critical aspect of cellular proliferation, differentiation, and transformation. In many cell types, the differentiation process is accompanied by a loss of proliferative capability, so that terminally differentiated cells become postmitotic and no longer progress through the cell cycle. In the experiments described here, the ocular lens has been used as a system to examine the role of the retinoblastoma protein (pRb) family in regulation of the cell cycle during differentiation. The ocular lens is an ideal system for such studies, since it is composed of just two cell types: epithelial cells, which are capable of proliferation, and fiber cells, which are postmitotic. In order to inactivate pRb in viable mice, genes encoding either a truncated version of simian virus 40 large T antigen or the E7 protein of human papillomavirus were expressed in a lens-specific fashion in transgenic mice. Lens fiber cells in the transgenic mice were found to incorporate bromodeoxyuridine, implying inappropriate entry into the cell cycle. Surprisingly, the lens fiber cells did not proliferate as tumor cells but instead underwent programmed cell death, resulting in lens ablation and microphthalmia. Analogous lens alterations did not occur in mice expressing a modified version of the truncated T antigen that was mutated in the binding domain for the pRb family. These experimental results indicate that the retinoblastoma protein family plays a crucial role in blocking cell cycle progression and maintaining terminal differentiation in lens fiber cells. Apoptotic cell death ensues when fiber cells are induced to remain in or reenter the cell cycle.

Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens

1991 ◽  
Vol 11 (12) ◽  
pp. 5968-5976
Author(s):  
J D Chen ◽  
T Van Dyke
Keyword(s):  
Transgenic Mice ◽  
Choroid Plexus ◽  
Simian Virus 40 ◽  
Regulatory Elements ◽  
Simian Virus ◽  
T Antigen ◽  
Rapid Expansion ◽  
Morphological Transformation ◽  
Large Tumor ◽  
Lymphotropic Papovavirus

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis.

Gastric epithelial morphogenesis in normal and transgenic mice

1997 ◽  
Vol 272 (5) ◽  
pp. G1209-G1220 ◽  
Author(s):  
S. M. Karam ◽  
Q. Li ◽  
J. I. Gordon
Keyword(s):  
Parietal Cell ◽  
Cell Lineage ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Parietal Cells ◽  
Cellular Migration ◽  
Multipotent Stem Cells ◽  
Proliferative Zone ◽  
Beta Subunit Gene

The epithelium located in the corpus of the adult mouse stomach forms mucosal invaginations known as gastric units. Gastric units are populated by members of the pit, parietal, and neck-zymogenic cell lineages all of which are derived from multipotent stem cells. Gastric unit morphogenesis was examined in normal embryonic day 18 (E18) to postnatal day 28 (P28) FVB/N mice with electron microscopy and multilabel immunohistochemistry. E18 units appear as short, solid infoldings (primordial buds), 92% of whose cells represent pit, parietal, and neck cell precursors. Although the total number of cells per bud does not change from P1 to P7, immature cells decrease to 22% as differentiated pit, neck, and parietal cells appear. From P7 to P15, lineage precursors and their differentiated progeny increase and buds elongate. Between P15 and P21 the multipotent stem cell and its descendants are assembled into a distinct proliferative zone (isthmus) located in the midportion of each unit, and cellular migration-differentiation programs become compartmentalized. To examine the role of parietal cells in regulating gastric unit morphogenesis, nucleotides -1035 to +24 of the mouse H(+)-K(+)-adenosinetriphosphatase beta-subunit gene were used to express simian virus 40 large T antigen (SV40 TAg) exclusively in this lineage. SV40 TAg amplified the normally rare pre-parietal cell and disclosed a pre-parietal cell precursor. Pre-parietal cells and their precursors were the predominant cells in E18-P1 transgenic buds. At later stages of development (P1-P28) there was a block in differentiation of pre-parietal to mature parietal cells, a decrease in neck cells, and a marked depletion of zymogenic cells. These findings suggest that members of the parietal cell lineage are the source of instructions that affect the neck-zymogenic cell lineage, even before the gastric unit is compartmentalized into its anatomically distinct pit, isthmus, neck, and base regions.

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