Altered Bicarbonate Reabsorption in the Pancreas of Reserpine-Treated Rabbits—a Model for Cystic Fibrosis

Shiffman, Mitchell L.; Spitzer, Robert J.; Swender, Phillip T.; Galey, William R.

doi:10.1203/00006450-198306000-00013

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…The recent development of the CF pig (Rogers et al 2008b, 2008c) and ferret (Li et al 2006; Sun et al 2008) have provided additional animal models that can potentially be used to elucidate CF pathology further and to develop therapies for CF. The rabbit is also an excellent candidate for an animal model of CF, because of the anatomical, genetic and biochemical similarities between the rabbit and the human and because of their gestation time and reproductive ability (Bosze et al 2003; Chen et al 2001; Diamond et al 1991; Fan and Watanabe 2003; Shiffman et al 1983). Both the phylogenetic nature of the rabbit and its physiology and anatomy make the rabbit a relevant model for the biochemical, molecular and physiological characterization of CF pathology and for the development of CF therapies (Vuillaumier et al 1997; Zeitlin et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Semir

Maurisse

et al. 2012

Cell Tissue Res

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The prospect of developing large animal models for the study of inherited diseases, such as cystic fibrosis (CF), through somatic cell nuclear transfer (SCNT) has opened up new opportunities for enhancing our understanding of disease pathology and for identifying new therapies. Thus, the development of species-specific in vitro cell systems that will provide broader insight into organ- and cell-type-specific functions relevant to the pathology of the disease is crucial. Studies have been undertaken to establish transformed rabbit airway epithelial cell lines that display differentiated features characteristic of the primary airway epithelium. This study describes the successful establishment and characterization of two SV40-transformed rabbit tracheal epithelial cell lines. These cell lines, 5RTEo- and 9RTEo-, express the CF transmembrane conductance regulator (CFTR) gene, retain epithelial-specific differentiated morphology and show CFTR-based cAMP-dependent Cl− ion transport across the apical membrane of a confluent monolayer. Immunocytochemical analysis indicates the presence of airway cytokeratins and tight-junction proteins in the 9RTEo- cell line after multiple generations. However, the tight junctions appear to diminish in their efficacy in both cell lines after at least 100 generations. Initial SCNT studies with the 9RTEo- cells have revealed that SV40-transformed rabbit airway epithelial donor cells can be used to generate blastocysts. These cell systems provide valuable models for studying the developmental and metabolic modulation of CFTR gene expression and rabbit airway epithelial cell biology.

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Section: Introductionmentioning

confidence: 99%

Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Semir

Maurisse

et al. 2012

Cell Tissue Res

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Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

Weizman

1996

Digest Dis Sci

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Plasma immunoreactive cationic trypsin (ogen) is elevated in cystic fibrosis during early infancy, before exocrine pancreatic insufficiency is fully developed. The recently developed cystic fibrosis mouse model carrying a mutated gene presents only minor pathologic findings in the pancreas. However, the reserpinized rat model shows cystic fibrosis-like defects in various exocrine glands, including the exocrine pancreas. Plasma immunoreactive cationic trypsin (ogen) has not been studied yet in this model. The present study explored the plasma immunoreactive cationic trypsin (ogen) pattern and possible mechanisms in this rat model. Plasma immunoreactive cationic trypsin (ogen) (RIA), pancreatic juice volume, protein, and trypsin, and pancreas weight were determined in rats treated with reserpine (0.5 mg/kg/day subcutaneously) for four or seven days, following cerulein stimulation (5 micrograms/kg/dose intraperitoneally), versus pair-fed controls. The first of four consecutive 30 min periods revealed peak values in all parameters. Four-day reserpine-treated rats demonstrated significantly higher plasma immunoreactive cationic trypsin (ogen) levels (167.3 +/- 12.8 vs 88.9 +/- 6.1 ng/ml; P < 0.0001) with similar values of pancreatic juice trypsin (8.2 +/- 2.4 vs 6.6 +/- 1.8 units/mg protein; P = NS) and volume (5.6 +/- 1.3 vs 4.2 +/- 1.6 mg/min/g pancreas; P = NS), compared to controls. Rats treated with reserpine for seven days revealed significantly lower values of plasma immunoreactive cationic trypsin (ogen) (39.2 +/- 8.4 vs 66.8 +/- 4.9 ng/ml; P < 0.001), pancreatic juice trypsin (1.9 +/- 0.3 vs 3.2 +/- 0.9 units/mg protein; P < 0.001) and volume (1.6 +/- 0.7 vs 3.1 +/- 0.6 mg/min/g pancreas; P < 0.001) compared to controls. We conclude that the reserpinized rat model resembles human cystic fibrosis as to elevated plasma immunoreactive cationic trypsin (ogen) before exocrine pancreatic insufficiency is fully developed. Since exocrine pancreatic volume secretion is intact at this stage, the mechanism of elevated plasma immunoreactive cationic trypsin is probably not due to ductular obstruction. We suggest that this model be studied further in order to investigate other possible mechanisms.

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Altered Bicarbonate Reabsorption in the Pancreas of Reserpine-Treated Rabbits—a Model for Cystic Fibrosis

Cited by 2 publications

References 14 publications

Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

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