Transgenic mouse lines with ectopic expression of  -1, 3-galactosyltransferase: production and characteristics

Ikematsu, Shinya; Kaname, Tadashi; Ozawa, Masayuki; Yonezawa, Suguru; Satô, Eiichi; Uehara, F; Obama, Hiroya; Yamamura, Ken‐ichi; Muramatsu, Takashi

doi:10.1093/glycob/3.6.575

Cited by 32 publications

(11 citation statements)

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“…Moreover, failure in the regulation of PAF metabolism has been suggested to elicit premature delivery and infertility (Narahara et al ., 1995; Toyoshima et al ., 1995). Expression of the PAFR transgene in the early embryonic stage can be deduced from studies of transgenic mice, using the same expression unit (Ikematsu et al ., 1993; Araki et al ., 1995). A fraction of 55‐H transgenic mice, despite the restricted pattern of transgene expression, may not survive gestation (Table II).…”

Section: Discussionmentioning

confidence: 99%

Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor

et al. 1997

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Although platelet-activating factor (PAF) has been shown to exert pleiotropic effects on isolated cells or tissues, controversy still exists as to whether it plays significant pathophysiological roles in vivo. To answer this question, we established transgenic mice over-expressing a guinea-pig PAF receptor (PAFR). The transgenic mice showed a bronchial hyperreactivity to methacholine and an increased mortality when exposed to bacterial endotoxin. An aberrant melanogenesis and proliferative abnormalities in the skin were also observed in the transgenic mice, some of which spontaneously bore melanocytic tumors in the dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for studying the basic pathophysiology of bronchial asthma and endotoxin-induced death, and screening of therapeutics for these disorders. Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo.

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Section: Discussionmentioning

confidence: 99%

Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor

et al. 1997

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“…Moreover, even the presence of an actin promoter behind CMVp still leads to high pancreas expression (Akagi et al, 1997;Fukuchi et al, 1996;Igeta et al, 1997;Imai et al, 1999;Shoji et al, 1998). Pancreas expression was not examined in another two studies where the same promoter construct was used to direct transgene expression in vivo (Ikematsu et al, 1993;Sawicki et al, 1998). We therefore favor the explanation alluded to above that quantitation and special consideration for the abundance of enzymes (ribonucleases and proteases) in the pancreas would have revealed dominant expression in the pancreas for all of the versions of CMVp used.…”

Section: Figmentioning

confidence: 99%

Predominant Transgene Expression in Exocrine Pancreas Directed by the CMV Promoter

Zhan

Brady

Johnston

et al. 2000

DNA and Cell Biology

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The enhancer/promoter of the human cytomegalovirus gene encoding the major immediate-early protein (CMVp) is reputed to be one of the strongest and most promiscuous regulatory elements for directing transcription of heterologous genes in vitro. However, transgene expression under the promoter in adult transgenic mice is often more restricted. We selected a CMVp segment from position -350 to +59 to control expression of transgenes for two secretory fusion proteins. Expression was analyzed by immunohistology staining and quantified by Northern blot, Western blot, and ELISA of secretions from explanted tissues. In all six lines of transgenic mice, the highest expression of transgenes at the mRNA and protein level was observed in the exocrine tissue of the pancreas, although the levels of expression varied among the lines. The results indicate not only that CMVp is not a universal promoter in vivo but indeed that it can be relatively specific for the exocrine pancreas, where expression of the gene it controlled was consistently very high.

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“…The enzyme responsible for linear B synthesis, α3-Gal-transferase, is not expressed in humans but a pseudogene for the enzyme does exist [Joziasse et al, 1991]. Transgenic mice overexpressing the enzyme appear to develop normally (table 4) [Ikematsu et al, 1993].…”

Section: Synthesis Of Terminal Structuresmentioning

confidence: 99%

Glycoproteins and Their Relationship to Human Disease

Brockhausen

Schutzbach

Kuhns

1998

Cells Tissues Organs

167

105

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Glycoproteins are proteins that carry N- and O-glycosidically-linked carbohydrate chains of complex structures and functions. N-glycan chains are assembled in the endoplasmic reticulum and the Golgi by a controlled sequence of glycosyltransferase and glycosidase processing reactions involving dolichol intermediates. The assembly of O-glycans occurs in the Golgi and does not involve dolichol. For most reactions, families of glycosyltransferases exist; the expression of the individual enzymes within a family is often subject to complex regulation. The biosynthesis of N- and O-glycan is controlled at the level of gene expression, mRNA, enzyme protein activity and localization, and through substrate and cofactor concentrations at the site of synthesis. This complex regulation results in many hundreds of structures, the range of which varies in different species, cell types, tissue types, states of development and differentiation. In diseased cells, the relative proportions of these structures are often characteristically different from normal, and may be useful for the assessment of the stage of the disease and for diagnosis. Knowledge of disease-specific glycoprotein structures and their functions may be used therapeutically, in immunotherapy, in blocking cell adhesion or interfering with other binding or biological processes. Recently, some of the mechanisms underlying glycoprotein alterations in disease have been elucidated. This opens the possibility of an active interference in the disease process. The functions of glycans in diseased cells will become more clear with the tools of molecular biology and transgenic animal models.

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Transgenic mouse lines with ectopic expression of -1, 3-galactosyltransferase: production and characteristics

Cited by 32 publications

References 0 publications

Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor

Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor

Predominant Transgene Expression in Exocrine Pancreas Directed by the CMV Promoter

Glycoproteins and Their Relationship to Human Disease

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