Comparative Study of Circadian Variation in Numbers of Peripheral Blood Cells among Mouse Strains: Unique Feature of C3H/HeN Mice

Abstract

Circadian variations in circulating blood cells have been recognized in various species.1) Periodic changes in the numbers of circulating cells in the peripheral blood might be the result of multiple factors such as the distribution between the circulating and marginal cell compartment among the tissues and organs of the body, influx from storage sites, cell proliferation, release of cells formed de novo into the circulation, as well as cell destruction and removal.2) The underlying mechanisms of circadian changes in circulating blood cells have not been fully elucidated, but the numbers of monocytes, natural killer (NK) cells, T and B cells, red blood cells fluctuate in a circadian manner.3-6) Thus, to study the hematological aspect such as immune function, anti-tumor activities and hematopoiesis, circadian rhythms in the numbers of circulating blood cells must be considered.Animal models are revolutionary tools for chronobiological studies that provide some obvious benefits. Experiments can be conducted in animals that would not be feasible in the humans, and genetic background as well as most environmental factors can be controlled. Such models have served as powerful tools for understanding the circadian rhythms of various biological parameters. However, the effect of the difference of genetic backgrounds on circadian rhythmicity of peripheral blood cells has not been studied in detail.In most inbred mouse strains except for the C3H, a genetic defect in the rate-limiting enzyme N-acetyl transferase blocks the production of the pineal melatonin.7) Interestingly, the number of circulating WBCs is sensitive to photoperiod via melatonin-mediated effects.8) Therefore, the initial goal of the present study was to test the hypothesis that the absence of a circadian melatonin rhythm in the circulation affects the circadian profile of the circulating blood cells.On the other hand, genetically engineered animals, such as transgenic and knockout mice are indispensable to elucidating the molecular mechanisms of many physiological functions. To breed knockout mice for investigations of these functions, parental or backcrossed strains must be appropriately selected. Although many knockout mouse lines have been generated and many physiological functions have been observed in vivo, the effect of the genetic background of strains has not always been considered. Consequently, a comparison of numbers of blood cells and their circadian rhythms in several strains of mice should provide useful information for experimentation using these mouse models.In this study, we observed changes in the numbers of circulating WBCs and RBCs in Jcl:ICR, BALB/cA, C57BL/6J and C3H/HeN mice throughout the day to obtain fundamental information about strain differences in the number of peripheral circulating blood cells and their circadian rhythms. We also examined the plasma concentrations of CS and EPO in these strains of mice that related to the numbers of circulating WBSs and RBCs, respectively. The present observations should provide basic info...

Quantitative Analysis of Mechanisms That Govern Red Blood Cell Age Structure and Dynamics during Anaemia

“…Our data and other work [44] suggest diurnal oscillations in Epo concentration in mice. It is therefore suggestive that diurnal oscillations in Epo could cause oscillations in production rate.…”

SIRT1 is dispensable for function of hematopoietic stem cells in adult mice

“…In addition to markedly decreased hematocrit in the old group, which is consistent with a study showing SIRT1 knockouts to be anemic due to decreased erythropoietin production in the liver and kidneys, 20 middle-aged and old SIRT1 Ϫ/Ϫ mice exhibited significant leukocytosis ( Figure 1B). Lymphocytosis and neutrophilia in SIRT1-deficient mice might reflect the perturbation of physiologic diurnal fluctuations in leukocyte counts, 21,22 which is consistent with the proposed role of SIRT1 in the regulation of circadian rhythms, 23,24 as well as possible dysregulation of cellular NAD ϩ supplies, which have been implicated directly in myeloid differentiation. 25 The young group, which exhibited markedly increased mortality, did not demonstrate any deficiencies in mature cell production, making hematopoietic failure an unlikely cause of premature death in this age group.…”

Congenic Fine-Mapping Identifies a Major Causal Locus for Variation in the Native Collateral Circulation and Ischemic Injury in Brain and Lower Extremity

“…However, the conclusion remains uncertain because, compared to B6 mice, C3H/HeJ have smaller collateral diameters, trend smaller in number, 18,63 and have lower blood pressure 64 and hemoglobin content than B6. 65, Mouse Phenome Database These differences are relevant because oxygen delivery across a collateral network after occlusion is proportional to [collateral number × diameter ^4 × arterial pressure×arterial oxygen content]. Thus, even a “small” reduction in collateral extent in the C3H/HeJ strain would result in a significantly greater infarct volume after MCAO.…”