Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 4: Mice

DOI: 10.29296/2618723X-2021-03-08

M.V. Miroshnikov, ORCID 0000-0002-9828-3242;
M.N. Makarova, ORCID 0000-0003-3176-6386

RMC «Home оf Pharmacy»
188663, Russia, Leningrad obl., Vsevolozhsky district, Kuzmolovsky t.s., Zavodskaya st. 3-245
Е-mail: [email protected]

Keywords: assessment of the clinical state of laboratory animals blood serum preclinical stage biological system

For citation:

Miroshnikov M.V., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 4: Mice. Laboratory Animals for Science. 2021; 3.


This article presents the results of the study and analysis of reference intervals of biochemical parameters of the blood of mice – one of the key test systems used at the preclinical stage of drug research. The data were obtained at the center of Scientific-Production Organisation «Номe of Pharmacy» in the period from January 2018 to December 2019 during the monitoring of animal health. The analyzed array contained data from 100 males and 100 females (non-pregnant and non-fertile females). During the adaptation period and subsequent experiments, the animals were kept in the same standard vivarium conditions: air temperature 22–26oC, relative humidity 40–75%, 12-hour daylight. The animals were fed in accordance with Directive 2010/63/EU of the European Parliament and of the Council of the European Union of September 22, 2010 on the protection of animals used for scientific purposes. The study was carried out in compliance with the principles of the European Convention for the Protection of Vertebrate Animals Used for Experiments and Other Scientific Purposes (Strasbourg, 1986) in accordance with the rules of good laboratory practice. The determination of biochemical parameters for all animals was carried out under equal conditions using analytical methods adopted in our testing center. The following parameters were determined in the blood serum of mice: creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cholesterol, triglycerides, total protein, albumin, glucose and total bilirubin. The data presented in the article indicate the need for periodic review of the reference intervals of laboratory animals used in experiments. The data obtained during the study confirm the need to create in-laboratory reference intervals in each specialized testing center not only for the mouse test system, but also for each animal species used in preclinical experiments, for a more accurate and detailed assessment of the clinical condition of the studied animals. The obtained reference intervals of the considered indicators correlate well with similar indicators from literary sources, which indirectly indicates their reliability.

Full text avaliable in Russain only 

Author’s Contribution

Miroshnikov M.V. – collection and systematization of material, statistical processing of the results, analysis and interpretation of the results, writing, editing text.
Makarova M.N. – idea, approval of the final version of the paper.

Conflict of interest

The authors declare that there is no conflict of interest.


  1. José M., Edelman E.R. From nonclinical research to clinical trials and patient-registries: challenges and opportunities in biomedical research // Revista Española de Cardiología (English Edition). – 2017. – P. 70. – №. 12. – P. 1121-1133. doi: 10.1016/j.rec.2017.07.008.
  2. Войтенко Н.Г., Макарова М.Н., Ковалева М.А. Вариабельность биохимических показателей крови и установление референсных интервалов в доклинических исследованиях. Сообщение 2: кролики //Лабораторные животные для научных исследований. – 2020. – №. 2. – С. 3-10. [Voitenko N.G., Makarova M.N., Kovaleva M.A. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 2: Rabbits // Laboratory animals for scientific research. – 2020. – №. 2. – P. 3-10. (In Russ.)].
  3. Andrade E.L., Bento A.F., Cavalli J. Non-clinical studies in the process of new drug development-Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies // Brazilian journal of medical and biological research. – 2016. – Vol. 49. – P. 1-19. doi: 10.1590/1414-431X20165646.
  4. Васильев А.Н., Ниязов Р.Р., Гавришина Е.В. Драницына М.А., Куличев Д.А. Проблемы планирования и проведения доклинических исследований в Российской Федерации //Ремедиум. Журнал о российском рынке лекарств и медицинской технике. – 2017. – №. 9. – С. 6-19.[ Vasil'ev A.N., Niyazov R.R., Gavrishina E.V. Dranitsyna M.A., Kulichev D.A. Problems of planning and conduct of preclinical trials in the russian federation//Remedium. Zhurnal o rossijskom rynke lekarstv i medicinskoj tekhnike. – 2017. – №. 9. – P. 6-19 (In Russ.)].
  5. Mazzaccara C., Labruna G., Cito G. Age-related reference intervals of the main biochemical and hematological parameters in C57BL/6J, 129SV/EV and C3H/HeJ mouse strains // PloS one. – 2008. – V. 3. – №. 11. – P. e3772. doi: 10.1371/journal.pone.0003772
  6. Quimby F.W., Luong R.H. Clinical chemistry of the laboratory mouse // The mouse in biomedical research. – 2007. – P. 171-216.
  7. Комарова Е.Ф., Коробейникова Е. П., Ванжа Л. В. Оценка противоопухолевой активности фармацевтической субстанции эноксифол на модели экспериментальной опухоли легкого // Злокачественные опухоли. – 2017. – №. Спецвыпуск 1. [Komarova E F., Korobeynikova E.P., Vanzha L.V, Ocenka protivoopuholevoj aktivnosti farmacevticheskoj substancii enoksifol na modeli eksperimental'noj opuholi legkogo //Zlokachestvennye opuholi. – 2017. – №. Specvypusk 1. (In Russ.)].
  8. Спасов А.А., Косолапов В.А., Бабков Д.А. Активаторы глюкокиназы-перспективный класс противодиабетических средств // Проблемы эндокринологии. – 2018. – Т. 64. – №. 3. – С. 180-187. [Spasov A.A., Kosolapov V. A., Babkov D.A. Glucokinase activators – a promising class of antidiabetic drugs//Problems of endocrinology. – 2018. – Vol. 64. – №. 3. – P. 180-187. (In Russ.)].
  9. Maltsev D.V., Spasov A.A., Yakovlev D.S. Searching for new anxiolytic agents among derivatives of 11-dialkylaminoethyl-2, 3, 4, 5-tetrahydrodiazepino [1, 2-a] benzimidazole // European Journal of Pharmaceutical Sciences. – 2021. – Vol. 161. – P. 105792.
  10. Спасов А.А., Мальцев Д.В., Мирошников М.В. Антидепрессивная активность и потенциальные механизмы действия производного диазепинобензимидазола ДАБ-19 // Экспериментальная и клиническая фармакология. – 2020. – Т. 83. – №. 4. – С. 31-36. [Spasov A.A., Mal'tsev D.V., Miroshnikov M.V. The antidepressant activity of diazepinobenbenzimidazole derivative dab-19 and its potential mechanisms of action // Problems of endocrinology. – 2018. – Vol. 64. – №. 3. – P. 180-187 (In Russ.)].
  11. Titlow W.B., Lee C.H., Ryou C. Characterization of toxicological properties of L-lysine polymers in CD-1 mice // Journal of microbiology and biotechnology. – 2013. – Vol. 23. – №. 7. – P. 1015-1022.
  12. ГОСТ Р 53022.2-2008. Технологии лабораторные клинические. Требования к качеству клинических лабораторных исследований. Часть 2. Оценка аналитической надежности методов исследования (точность, чувствительность, специфичность) М., 2008. [GOST R 53022.2-2008 Tekhnologii laboratornye klinicheskie. Trebovaniya k kachestvu klinicheskih laboratornyh issledovanij. CHast’ 2. Ocenka analiticheskoj nadezhnosti metodov issledovaniya (tochnost’, chuvstvitel’nost’, specifichnost’) M., 2008. (In Russ.)].
  13. Кишкун, А.А. Руководство по лабораторным методам диагностики / Москва :ГЭОТАР-Медиа, 2009. – 800 с. [Kishkun A. A. Guide to laboratory diagnostic methods: for doctors and paramedics providing the first medical aid. Help / Moscow - GEOTAR-media, 2009.-800 p. (In Russ.)].
  14. Лифшиц В.М., Сидельникова В.И. Биохимические анализы в клинике / Москва: ООО" Издательство" Триада", 2006. – С. 216 [Lifshits V. M., Sidelnikova V. I. Biochemical analyses in the clinic. / Moscow " Publishing House "Triada", 2006. – p. 216 (in Russ.)].
  15. Serfilippi L.M., Pallman D.R., Russell B. Serum clinical chemistry and hematology reference values in outbred stocks of albino mice from three commonly used vendors and two inbred strains of albino mice // Journal of the American Association for Laboratory Animal Science. – 2003. – Vol. 42. – №. 3. – P. 46-52.
  16. Аледо М.М., Калганов С.А. Биохимические показатели крови мышей при введении в рацион ГМ-кукурузы //В мире научных открытий: материалы III Международной студенческой научной конференции. 22-23 мая 2019 г.-Ульяновск: УлГАУ, 2019.-Т. V, Ч. 1. – УлГАУ, 2019. [Aledo M.M., Kalganov S.A., Karmeeva Y.S. Biochemical indicators of laboratory mice blood when feeding them gm-corn // V mire nauchnyh otkrytij: materialy III Mezhdunarodnoj studencheskoj nauchnoj konferencii. 22-23 maya 2019 g.-Ul'yanovsk: UlGAU, 2019.-T. V, CH. 1. – UlGAU, 2019. (In Russ.)].
  17. Charles River Information. CD-1 IGS Mouse Model Information Sheet. – 2013. – URL.: (дата обращения 06.2021 г.)

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