Model-based exploration of hypokalemia in dairy cows

Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia—reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin—by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments

Model-based exploration of hypokalemia in dairy cows

Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia—reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin—by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments.publishedVersio

Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

Background: A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoim)Hgumouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1) two inbred mutant mouse strains CF/1-CftrTgH(neoim)Hguand CF/3-CftrTgH(neoim)Hguhad been generated using strict brother × sister mating. CF/1-CftrTgH(neoim)Hguand CF/3-CftrTgH(neoim)Hgumice were fertile and showed normal growth and lifespan. In this work the CftrTgH(neoim)Hguinsertional mutation was backcrossed from CF/3-CftrTgH(neoim)Hguonto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the Cftr mutation and the genetic background on the disease phenotype of the cystic fibrosis mutant mice. Clinical and electrophysiological features of the two congenic strains were compared with those of CF/1-CftrTgH(neoim)Hguand CF/3-CftrTgH(neoim)Hguand wild type controls. Results: Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-CftrTgH(neoim)Hgu, CF/3-CftrTgH(neoim)Hgu, D2.129P2(CF/3)-CftrTgH(neoim)Hguand B6.129P2(CF/3)-CftrTgH(neoim)Hguexhibited normal life expectancy. Growth of congenic cystic fibrosis mice was comparable with that of wild type controls. All mice but D2.129P2(CF/3)-CftrTgH(neoim)Hgufemales were fertile. Short circuit current measurements revealed characteristic response profiles of the HsdOla:MF1, DBA/2J and C57BL/6J backgrounds in nose, ileum and colon. All cystic fibrosis mouse lines showed the disease-typical hyperresponsiveness to amiloride in the respiratory epithelium. The mean chloride secretory responses to carbachol or forskolin were 15-100% of those of the cognate wild type control animals. Conclusion: The amelioration of the clinical features and of the basic defect that had emerged during the generation of CF/3-CftrTgH(neoim)Hgumice was retained in the congenic mice indicating that the Cftr linkage group or other loci shared between the inbred strains contain(s) the major modifier(s) of attenuation of cystic fibrosis symptoms