Mice (Mus Musculus)

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    C57BL/6, female, 22 weeks old

    Mice are often used in scientific research because they share many genetic and physical traits with humans. However, since mice and humans evolved in different environments, they have distinct differences. While both species have certain shared biological processes, their reactions to experiments can vary significantly. Mice are great for studying shared biological traits and understanding how different species develop from common genes. But when it comes to mimicking human diseases, mice might not always be the best models since the connections between genes and diseases can vary between humans and mice. So, while mice are helpful in research, it's essential to consider both their similarities and differences with humans. [1]

    Benefits for Longevity Research

    Development of mice in the first 2 weeks of life [2]

    Mice are beneficial for longevity research for several reasons:

    1. Short Lifespan: Mice have a relatively short lifespan, typically 2-3 years. This allows researchers to study the entire life cycle of the organism in a condensed time frame, making it feasible to observe the effects of interventions on aging within a realistic research period.
    2. Genetic Manipulability: Mice genomes can be easily manipulated, allowing scientists to create genetically modified strains to study specific genes or pathways related to aging.
    3. Conserved Aging Mechanisms: Many biological processes related to aging are conserved between mice and humans. This means that discoveries in mice often provide insights into human aging and potential interventions.
    4. Cost-Effective: Maintaining mice in a research setting is less expensive compared to larger animals. This makes it economically feasible to run long-term studies with large sample sizes.
    5. Reproducibility: Mice have relatively short reproductive cycles and produce numerous offspring. This allows for studies across multiple generations in a short time.
    6. Controlled Environment: It's easier to control external factors such as diet, environment, and exposure to substances in mice, ensuring that the observed effects are due to the interventions and not external variables.
    7. Rich Data Sets: Due to the extensive use of mice in research, there's a wealth of pre-existing data available. This enables researchers to compare and contrast findings from longevity studies with data from other domains.
    8. Ethical Considerations: While all animal research has ethical considerations, the use of shorter-lived organisms like mice often presents fewer ethical complexities than the use of longer-lived animals, especially primates.

    Mouse Strains Relevant for Longevity Research

    Strain Name Description Key Traits Use in Longevity Research
    C57BL/6 Most commonly used inbred strain High susceptibility to diet-induced obesity Often used as a reference strain in aging studies
    Ames Dwarf Mutant strain with deficiency in growth hormone, prolactin, and thyroid-stimulating hormone Extended lifespan; reduced tumor incidence Key model in studying hormonal effects on aging
    Snell Dwarf Similar to Ames Dwarf with pituitary deficiencies Extended lifespan; improved insulin sensitivity Used to study hormonal regulation and aging
    SAM (Senescence-Accelerated Mouse) Group of related strains with accelerated aging Varies by substrain (e.g., SAMP8 shows early cognitive decline) Widely used in aging research to study rapid aging effects
    ApoE−/− (Apolipoprotein E-deficient) Mutant strain deficient in ApoE protein Prone to cardiovascular diseases; develops atherosclerosis Widely used in cardiovascular research, providing insights into age-related cardiovascular diseases
    C3H Inbred strain with a propensity for certain tumors Prone to mammary tumors; used in cancer research Relevant in longevity research, especially in studies linking aging and cancer
    B6C3F1 Hybrid strain derived from C57BL/6 and C3H High tumor incidence in old age Used in carcinogenicity and aging studies
    DBA/2 Inbred strain known for early age-related hearing loss High bone density; resistant to diet-induced obesity Used in sensory aging studies, particularly hearing
    BALB/c Inbred strain with known susceptibility to certain cancers High levels of anxiety-like behavior Used in cancer and aging studies
    ICR (Institute of Cancer Research) Outbred strain Good reproductive performance; used as general multipurpose strain Often used as a control strain in various research, including aging
    UM-HET3 Hybrid strain resulting from specific crossbreeding Exhibits heterosis; long lifespan potential Utilized in studies examining the genetic basis of aging and longevity

    Differences Between Human and Laboratory Mice

    Feature Mice Human Difference
    Lifespan ~2-3 years ~80 years (average) ~40x
    Reproductive Age Start ~6-8 weeks ~12-15 years ~100x
    Growth Rate 2-3 months to maturity 18-25 years to reach full adult size ~90x to ~100x
    Genome ~20,000-25,000 protein-coding genes ~20,000-25,000 protein-coding genes differences in some gene families and pathways
    Genome Size ~2.7 billion base pairs ~3.2 billion base pairs
    Number of Chromosomes 40 (20 pairs) 46 (23 pairs)
    Heart Rate ~500-700 beats/minute ~60-100 beats/minute ~8x
    Metabolic Rate Faster Slower Variable (often >10x)
    Bone Density Decline Begins around 1 year Begins in late 20s ~25x
    Body Weight 20-40 g (female) & 25-45 g (male) Average 62 kg (female) & 77 kg (male) ~2000x (average)
    Brain Size ~0.4 cm³ ~1400 cm³ ~3500x
    Blood Volume ~2 ml ~5 liters ~2500x
    Caloric Restriction Response Increases longevity Increases longevity
    Diet Omnivorous, often fed controlled diets in labs Omnivorous, varied diet
    Telomere Length Relatively longer in many cells Shorter in somatic cells
    Reproductive Cycle 4-5 days (Estrous cycle) ~28 days (Menstrual cycle) ~6x
    Pregnancy Duration ~19-21 days ~280 days ~14x
    Immune System Faster initial response, less memory-driven Slower response, memory-driven
    Drug Metabolism Faster drug metabolism due to differences in liver enzymes Slower drug metabolism
    Blood Cell Lifespan Red cells: ~40 days Red cells: ~120 days ~3x
    Allometric Scaling Correction Factor 3 37 ~12x

    See [2] for relating the ages of men and mice.

    See Also

    References

    1. Perlman RL: Mouse models of human disease: An evolutionary perspective. Evol Med Public Health 2016. (PMID 27121451) [PubMed] [DOI] [Full text] The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experimental interventions in ways that differ strikingly from humans. Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species. Mice are less reliable as models of human disease, however, because the networks linking genes to disease are likely to differ between the two species. The use of mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans.
    2. 2.0 2.1 Dutta S & Sengupta P: Men and mice: Relating their ages. Life Sci 2016. (PMID 26596563) [PubMed] [DOI] Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail.