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Timo Nevalainen University of Eastern Finland Kuopio, Finland

Timo Nevalainen University of Eastern Finland Kuopio, Finland

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Timo Nevalainen University of Eastern Finland Kuopio, Finland

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  1. Rodent biology Timo Nevalainen University of Eastern Finland Kuopio, Finland

  2. Origin • Mouse • house mouse (Mus musculus) • use started 1600’s, but increased during 1800’s with increasing research activity • Rat • Brown rat (Rattus norvegicus) came from Asia to Europe at the beginning of 1700’s • Black rat (Rattus rattus) has faded away

  3. Quiz: Rat or mouse? Quiz: Roof rat or Brown rat?

  4. Why chosen ? • Synonyms of disease and death, not connected to biomedical research • Small, economical and mammal • Easily adapted and tamed • Several common features with other mammals

  5. Reproduction

  6. Development of vertebrate embryos

  7. Life cycle of mouse

  8. Animal age vs. human age • Comparing rat’s to human’s age: How old is my rat in people years? • Aging in Mouse and Human Systems: A Comparative Study • AnAge Database • Translating time - across developing mammalian brains

  9. Mice: Heart rate = 306-700 beats/minute Respiratory rate = 85-200 breaths/minute Body temperature = 36.5 C Rats: Heart rate = 250 – 450 beats/minute Respiratory rate = 70-115 breaths/minute Body temperature = 36.5 C Vital Statistics

  10. Strains and Stocks • Inbred - developed out of brother-sister mating for 20 generations, producing 99% genetic homology. • Outbred stocks (random bred) are genetically heterozygous.

  11. White rat?

  12. Stock or strain ? • Wistar (albino), Sprague-Dawley (albino), Long-Evans origin (origin) • Outbreds are stocks • Inbred and other defined animals are strains

  13. AKR BALB/c C3H C57BL C57BL/10 C57BL/6 DBA/2 NZB AK C C3 B B10 B6 D2 ZB Most common inbred mouse strains and correct name

  14. Albinos, so what ? • c-locus albinism – melanin is missing • Melanocytes present, but because of absence of tyrosinase; no melanin is produced • Albinism results in changes of neuroanatomy, -physiology, metabolism and behavior • Creel. Pharmacology, Biochemistry and Behaviour 12:969-977, 1980

  15. Rat's vision Human, normal vision red-insensitive colorblind, faint color Normally-pigmented rats have blurry dichromatic vision with low color saturation Albino rats may see a very blurry, light-flooded world On a bright day, albino rats may be completely dazzled

  16. Albinism and vision • Albino rats can have retinal degeneration at low light intensities • More than 60 lux for 30 weeks in cage – albino rats are likely to be blind • Manage with other senses • Animal room light mainly for people, animals must be protected from excessive light

  17. What do rats see? • www.ratbehavior.org/images/HumanCam.mov • www.ratbehavior.org/images/RatCam.mov • www.ratbehavior.org/images/AlbinoRatCam.mov

  18. Coprophagy • rats and mice eat their own feces • Important for vitamin • Directly from anus – grid floor does not prevent • Preventing coprophagy decreases growth by 10-20% • Important in pharmacology with per os administration

  19. Full article

  20. Thermoregulation • No sweat glands • Cannot dissipate heat by sweating or panting • In extreme situation moist fur with saliva – can lead to dehydration • Poor heat tolerance • Usually change amount of circulation to hairless areas - tail

  21. Rat tail anatomy

  22. Diurnal rhythm • Rats and mice are nocturnal animals • Activity and eating during dark • Daytime mainly sleep • In research please note • Many hormones fluctuate considerably according to time • If want to study during activity, reverse the light cycle

  23. Metabolism and Body Scaling • Concept of METABOLIC SIZE. • Mice and rats have high surface area to body volume ratios. Volume: Surface Area: Low High High Low

  24. High surface area: Dissipate body heat Compensate with increase of Metabolic Rate Low surface area: Conserve body heat Compensate with decrease in Metabolic Rate Relationships of Metabolic Size

  25. Consequences from Metabolic Size: Scaling drug doses between species of different size (apart from species specific features). • Higher dose rates (mg/kg) in mice, rats than in larger species. • To use the “dog dose rate” in mice – risk of inefficacy. • To use the “mouse dose rate” in dogs – risk of toxicity.

  26. Do we house rodents right? • Care routines aim at hygiene • cage used to be an open space • Other things may be important to animals • Digging, nest making, gnawing • In open cage – walling effect • The more space – the better ?

  27. Do we feed rodents correctly ? • same chow for both rats and mice • same diet for breeding and maintenance • routine method = ad libitum • eat too much • become obese • shorter life span • more tumors • group housing and restricted feeding are not compatible

  28. Environmental Enrichment Lab strains of rats and mice kept under field conditions express wild rodent behaviors. Environmental enrichment – prefer nest boxes, nest material and gnawing materials. Effect of environmental enrichment on animals: exposure to complex experiences alter neuroanatomical parameters and chemistry associated with memory and learning. Animals exhibit greater adaptability.

  29. Rodent autopsy/anatomy websites Pathology and Autopsy of a Mouse 3D MRI Digital Atlas Database of Adult C57BL/6J Mouse Brain 

  30. Anatomy information on mouse www.ana.ed.ac.uk/anatomy/database/ www.informatics.jax.org/mgihome/GXD/gxdgen.shtml http://genex.hgu.mrc.ac.uk/Databases/Anatomy/new/home.shtml www.rodentia.com/wmc/domain_mouse.html www.hms.harvard.edu/research/brain/ www.hms.harvard.edu/research/brain/

  31. http://wholebraincatalog.org/

  32. Anatomy • Harderian gland (lacrimal) – • Tears contain porphyrin • Normal function of lubrication • Conditions of stress (non-specific) cause excess accumulation around eyes and nose.

  33. Teeth Overgrowth

  34. Gastrointestinal System Similarities: Stomach – glandular & aglandular regions Large cecum Pancreas diffuse Differences Rat – no gall bladder

  35. Urinary Urine : Mouse - 4X concentrated as man Rat – 2X concentrated as man Excrete urine 1-2 drops at a time. Pass urine when picked up – easy to collect a urine sample. Urine rich in proteins Allergenic! Exposure via dusts, contact with skin

  36. Pheromones • present in male mice urine • effects on reproduction • Lee-Boot effect: Females without males – estrus cycles is suppressed • Whitten effect: Male to a female group – estrus cycle synchronized • Bruce effect: Strange male into female group within 24h from mating – implantation prevented

  37. Estrus Detection • Both of these mice are in estrus – they are in different stages. • The mouse on the top would be chosen for an immediate breeding pair set up. • The mouse on the bottom is in an earlier stage of estrus.

  38. Estrus Detection Estrus Non-Estrus Note the swollen, moist Note the closed vaginal and open appearance to the opening and pale mucus vaginal opening; coloration membrane color. of mucus membranes is pale.

  39. Estrus vs. Non-Estrus * swollen vaginal tissue * no swelling evident * gaping vaginal opening * closed vaginal opening * moist tissues * dry tissues * bright pink/purple * pale mucus membranes mucus membranes