Abstract
BackgroundClinical chemical blood analysis including plasma electrolytes is routinely carried out for the diagnosis of various organ diseases. Phenotype-driven N-ethyl-N-nitrosourea (ENU) mouse mutagenesis projects used plasma electrolytes as parameters for the generation of novel animal models for human diseases.MethodsHere, we retrospectively evaluated the use of the plasma electrolytes calcium, chloride, inorganic phosphorus, potassium and sodium in the Munich ENU mouse mutagenesis project where clinical chemical blood analysis was carried out on more than 20,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in various plasma parameter levels.ResultsWe identified a small number of animals consistently exhibiting altered plasma electrolyte values. Transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of mutant lines for the parameters calcium and potassium. Published data from other phenotype-driven ENU projects also included only a small number of mutant lines which were generated according to altered plasma electrolyte levels.ConclusionThus, use of plasma electrolytes detected few mouse mutants in ENU projects compared to other clinical chemical blood parameters.
Highlights
Clinical chemical blood analysis including plasma electrolytes is routinely carried out for the diagnosis of various organ diseases
Physiologic plasma electrolyte values in C3HeB/ FeJ (C3H) mice In the Munich ENU mouse mutagenesis project, the values for the plasma electrolytes Ca, Cl, K, Na and P were first determined in about 200 male and 200 female threemonth-old wild-type C3H mice [13] and the 95% range of the values was defined to be physiologic [2]
We retrospectively evaluated the use of the plasma electrolytes Ca, Cl, K, Na and P in the clinical chemical blood analysis of the Munich ENU mouse mutagenesis project to detect dominant and recessive mutations leading to deviations in plasma levels
Summary
Clinical chemical blood analysis including plasma electrolytes is routinely carried out for the diagnosis of various organ diseases. Phenotype-driven N-ethyl-N-nitrosourea (ENU) mouse mutagenesis projects used plasma electrolytes as parameters for the generation of novel animal models for human diseases. A strategy for the genome-wide generation and search of novel diseaserelated alleles consists of the random chemical mutagenesis of a large number of animals followed by systematic screening for clinically relevant disease phenotypes. ENU mouse mutagenesis projects were established for the systematic, genome-wide, large-scale production and analysis of mouse mutants as model systems for inherited human diseases. They used appropriate routine procedures allowing the screening of large numbers of mice for a broad spectrum of parameters [4,5]. ENU-induced mice with the causative mutation already identified are successfully used in different areas of biomedical research ([6,7] and refs. therein)
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