A novel murine model of aging, Senescence-Accelerated Mouse (SAM)

doi:10.1016/0167-4943(94)90039-6

Archives of Gerontology and Geriatrics

Volume 19, Issue 2, September–October 1994, Pages 185-192

https://doi.org/10.1016/0167-4943(94)90039-6 Get rights and content

Abstract

Senescence-Accelerated Mouse (SAM) has been under development by our research team at Kyoto University since 1970, based on the AKR/J strain donated by the Jackson Laboratory in 1968. The SAM mouse has an accelerated senescence and age-associated pathologies such as senile amyloidosis, senile osteoporosis, degenerative joint disease, cataract, deficits in learning and memory, brain atrophy, hyperinflation of lungs, hearing impairment and so on. SAM research is advancing world-wide and attempts are being made to clarify fundamental mechanisms involved in primary aging processes, pathogenesis of age-associated pathologies and effective methods to modulate or ameliorate the advance of senescence and disease processes involved in age-associated pathologies.

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The position and size of the major cusps in mammalian molars are arranged in a characteristic pattern that depends on taxonomy. In humans, the cusp which locates distally within each molar is smaller than the mesially located cusp, which is referred to as “distal reduction”. Although this concept has been well-recognized, it is still unclear how this reduction occurs. Current study examined whether senescence-accelerating mouse prone 8 (SAMP8) mice could be a possible animal model for studying how the mammalian molar cusp size is determined.
SAMP8 mice were compared with parental control (SAMR1) mice. Microcomputed tomography images of young and aged mice were captured to observe molar cusp morphologies. Cusp height from cement-enamel junction and mesio-distal length of molars were measured. The statistical comparison of the measurements was performed by Mann-Whitney U test.
SAMP8 mice showed reduced development of the disto-lingual cusp (entoconid) of lower second molar when compared with SAMR1 mice. The enamel thickness and structure was disturbed at entoconid, and aged SAMP8 mice displayed severe wear of the entoconid in lower second molar. These phenotypes were observed on both sides of the lower second molar.
In addition to the general senescence phenotype observed in SAMP8 mice, this strain may genetically possess molar cusp phenotypes which is determined prenatally. Further, SAMP8 mice would be a potential model strain to study the genetic causes of the distal reduction of molar cusp size.
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Citation Excerpt :
SAMP8 mice develop normally up to 6 months of age, but exhibit accelerated senescence along with age-associated pathologic changes, behavioral alterations, and cognitive deficits, and a shortened lifespan of approximately 12 months compared with 2–3 years for other strains (Takeda et al., 1994). SAMP8 mouse is widely used as an animal model of human Alzheimer disease (Takeda et al., 1994). In this study, we used aged male SAMP8 mice (8 months old; n = 48).
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SAMP8 mice (8 months old) with either teeth intact or teeth extracted were raised in a standard or enriched environment for three weeks. Spatial learning and memory ability was evaluated in a Morris water maze test. The morphologic features of the myelin sheath and synapses in the hippocampus were investigated by electron microscopy.
Mice with tooth loss had a thinner myelin sheaths and shorter postsynaptic densities in the hippocampal CA1 region, and impaired hippocampus-dependent spatial learning ability. Exposure to an enriched environment ameliorated the hypomyelination and synaptic alterations, and spatial learning and memory impairments induced by tooth loss in aged SAMP8 mice.
Our findings indicate that an enriched environment ameliorates hippocampal hypomyelination and synapse morphologic abnormalities, as well as learning deficits induced by tooth loss in aged SAMP8 mice.
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It has been hypothesized that oxidative stress, which is an imbalance between endogenous levels of oxygen radicals and antioxidant defense systems, is the main cause of aging. Senescence-accelerated mouse prone 10 (SAMP 10), which is a strain of aging-promoting model mice, shows learning and memory impairment with age, and atrophy is observed in the cerebral cortex and limbic system. The oxygen radical production in SAM mice brain tissues increases with age. The slope of the age-dependent increase was steeper in SAMP10 than control mice. Antioxidant enzyme levels in the liver of SAMP10 were higher than those in the control mice at young age, but at old age, antioxidant enzyme levels were lower and/or similar to the levels of control mice. These results suggest that oxidative stress is strongly involved in the cause of senescence acceleration of SAMP10 and that SAMP10 is a model animal suitable for the study of normal aging.
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A novel murine model of aging, Senescence-Accelerated Mouse (SAM)

Abstract

J. Biol. Chem.

FEBS Lett.

Mech. Ageing Dev.

Exp. Eye Res.

Mech. Ageing Dev.

J. Nutr.

Physiol. Behav.

Mutat. Res.

Neuroscience

Bone

Mech. Ageing Dev.

Mech. Ageing Dev.

Bone

Bone Miner.

J. Nutr.

J. Nutr.

Mech. Ageing Dev.

Age-related morphological changes in the brains of Senescence-Accelerated Mouse (SAMP8)

Age related changes in the temporomandibular joint of the Senescence Accelerated Mouse (SAM): SAM-P/3 as a new murine model of degenerative joint disease

Am. J. Pathol.

Diseases of aging