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Frailty

Frailty Index of Deficit Accumulation

Rationale: Measures of neurobehavioral development, activity and arousal, motor function (coordination, balance, and muscle strength).

Instrument: Mouse cage observations.

Measures:

Alopecia: Inspect for signs of fur loss.
Loss of fur color: Note any change in fur color from black to grey or brown or white.
Dermatitis: Document skin lesions.
Loss of whiskers: Inspect the animal for signs of a reduction in the number of whiskers.
Coat condition: Inspect the animal for signs of poor grooming.
Piloerection: Observe the animal and look for signs of piloerection, in particular on the back of the neck.
Cataracts: Visual inspection of the mouse to detect opacity in the center of the eye.
Eye discharge/swelling: Visual inspection of the mouse to detect ocular discharge and swelling of the eyes.
Microphthalmia: Inspect eyes for size and changes
Corneal opacity: Visual inspection of the mouse to superficial white spots and/or clouding of the cornea.
Nasal discharge: Visual inspection of the mouse to detect nasal discharge.
Rectal prolapse: Grasp the mouse by the base of the tail to detect signs of rectal prolapse.
Penile/vaginal prolapse (male/female): Grasp the mouse by the base of the tail to detect signs of vaginal/uterine or penile prolapse.
Diarrhea: Visual inspection for soft, smeared stool around rectum
Body condition: Manually palpate the flesh/fat that covers the sacroiliac region (back and pubic bones).
Tumors: Observe for symmetry. Hold the base of the tail and manually examine mice for visible or palpable tumors.
Kyphosis: Visually inspect the mouse for curvature of the spine or hunched posture.
Gait disorders: Observe the freely moving animal to detect abnormalities such as hopping, wobbling, circling, wide stance and weakness.
Tremor: Observe the freely moving animal to detect tremor, both at rest and when the animal is trying to rear.
Breathing rate/depth: Observe the animal. Note the rate and depth of breathing as well as any gasping behavior.
Menace reflex: Move an object (cotton swab) towards the mouse’s face (between the eyes) 3 times. Record whether the mouse blinks in response
Tail stiffening: Grasp the base of the tail with one hand, and stroke the tail with a finger of the other hand. The tail should wrap freely around the finger when mouse is relaxed. Mouse should not pull
Vestibular disturbance: Hold the base of the tail and lower mouse towards the wire bar grid. Inspect for head tilt, spinning, circling, head tuck or trunk curling.
Vision loss (Visual Placing): Lower mouse towards a grid cage lid surface. Evaluate the position the mouse reaches towards the surface.
Distended abdomen: Hold the mouse in the supine position and observe abdomen distending below the rib cage over the hip bone areas.
Malocclusions: While the mouse is restrained in the supine position, gently expose the teeth with the non-cotton tip side of the cotton swap. Look for uneven, overgrown teeth.
Temperature: Measure body temperature with lubricated rectal thermometer.
Righting Reflex: From the restrained supine position (belly up) above the bedded arena (~25cm), quickly and briskly release the mouse and move the restraint hand away from the mouse. Normal response of the animal is to land on its feet.

Data Inference: Data from neurobehavioral/neurological tests can serve as criterion for inclusion in specific behavioral studies as well as guide the choice of behavioral tools to minimize potential confounds. Outcomes also provide a first measure of age-related phenotypes. Scores of 0, 0.5 and 1 are added up and divided by total number of parameters to produce a frailty index score.