Shuji Takeshita

Spontaneous age-associated amyloidosis in senescence-accelerated mouse (sam).

Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R). Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%). Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm. The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.

Cataract and other ophthalmic lesions in senescence accelerated mouse (SAM). Morphology and incidence of senescence associated ophthalmic changes in mice

In a murine model of accelerated senescence (SAM), grading score and incidence in cataract, periophthalmic lesions, opacity and ulcer of the cornea were determined in mice from 4 to 24 months of age. From 4 to 6 months of age, incidence and grading score of these four categories began to increase in both the accelerated senescence prone (SAM) and resistant series with normal aging, and these increases continued with aging. As compared with the resistant series, there was a higher incidence and grading score of the four categories and a higher rate of increase in the prone series. The prone 3 series in particular showed a much higher incidence and grading score on cataract, the rate being 27.5% and 70.6% at 12 and 16 months, respectively. Histologically, the cataract was classified into two types. In one, degeneration of lens fibers, disintegration of lens cortex, and at an advanced stage, liquefaction of the lens cortex and proliferation of the anterior lens epithelial cells occurred. In the other type, lens fibers lost their distinct shapes and a homogenous mass formed at the anterior and posterior superficial cortex. The anterior lens epithelial cells had shrunk. There was an opacity and ulcer of the cornea with keratitis and the corneal epithelium was lost in case of the latter. Periophthalmic lesions included catarrhal changes of the skin of the eyelids and face and blepharitis. There were no lesions specific to each of the prone and resistant series. Thus, SAM should prove to be a suitable murine model for investigation of age-related ophthalmic lesions, including cataract in humans.

A New Senile Amyloid Fibril Protein and Its Putative Precursor in Senescence Accelerated Mouse (SAM)

A new amyloid fibril protein was isolated from the livers of Senescence Accelerated Mice (SAM-P), a strain characterized by accelerated senescence and a high incidence of age-associated systemic amyloidosis. This 5,200 dalton amyloid protein “ASSAM” differs in amino acid composition from the amyloid protein of murine secondary amyloidosis. Sequence analysis revealed a blocked N-terminus. Double immunodiffusion tests showed no relationship between ASSAM and murine protein AA or immunoglobulin components.