![]() 7, 11, 23 The high number of influencing factors makes it difficult to define universally valid ‘normal values’. 2, 12, 27, 47 Furthermore, significant effects of housing conditions and experimental procedures have been reported for many clinical chemistry plasma analytes in mice. In addition to strain- and substrain-specific features, sex- and age-dependent differences in phenotypic traits have been described. Therefore not only strains but also substrains can demonstrate genetic discrepancies 28 that account for differences in findings between laboratories, 8, 19, 23, 40 structural phenotypes, 30 behavior, 39, 41, 43 and responses to different stimuli. During the 220 generations of evolution, the backgrounds of the C57BL/6J and C57BL/6N substrains separated from each other. The journey continued to various vendors, who currently offer several different but related mouse substrains, such as the C57BL/6NTac line, which was established in 1991 at F151. In 1951 at F32, this strain was passed to the NIH, and continued isolated breeding resulted in a new substrain, C57BL/6N. ![]() ![]() For example, C57BL/6 was established in 1921 at the Bussey Institute for Research in Applied Biology and, at F24 in 1948, traveled to the Jackson Laboratory (C57BL/6J). Within these strains, various substrains with specific genetic and phenotypic characteristics are available. ![]() 31 Widely used inbred mouse lines include several strains of C57BL/6 and C3H origin these mice are available from different internationally operating vendors. 3, 28, 29 The uniform genetic background of inbred mice improves standardization and helps researchers worldwide to compare their results with sufficient reproducibility, thereby minimizing the repetition of experiments. Such research typically involves the use of inbred strains, which are generated through at least 20 generations of brother×sister mating. The numbers of animals used are continuously rising ( ), and most of them are needed for pharmacology, oncology, toxicology, drug safety, forward and reverse genetic, and other studies. Mice are widely used as model organisms to investigate biologic mechanisms in health and disease but also to establish new diagnostic and therapeutic strategies. Our results support researchers interpreting clinical chemistry values from various mouse mutants and corresponding wild-type controls based on the examined strains and substrains. In addition, we include an overview of the literature that reports clinical chemistry values for wild-type mice of different strains. Significant effects of age and sex on these analytes were identified, and strain- or substrain- and sex-specific reference intervals for 90- to 135-d-old mice were calculated. The corresponding data sets of electrolytes (sodium, potassium, calcium, chloride, inorganic phosphate), lipids (cholesterol, triglyceride), and enzyme activities (ALT, AST, ALP, α-amylase) and urea, albumin, and total protein levels were analyzed. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable.
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