Biochemical and Genetic Characterization of Murine Senile Amyloidosis
We determined the primary structures of murine senile amyloid protein (ASSAM) which was isolated from the livers of accelerated senescence prone mice (SAM-P) and apo SASSAM, wnich has a common antigenicity with ASSAM in the serum, derived from slc:ICR mice. ASSAM consists of a single polypeptide chain of 78 amino acid residues, of which the amino-terminus is blocked with pyrrolidone carboxylic acid and the amino acid sequence of ASSAM differs from those of the known amyloid proteins. Apo SASSAM is the murine apolipoprotein (apo) A-II because high homology is present between the primary structures of apo SASSAM and human apo A-II. Sequence comparison between ASSAM and apo SASSAM revealed that ASSAM is an apo A-II variant with one amino acid substitution of glutamine for proline at position 5.
The apo A-II variant (Pro5→Gln) is present only in the serum of SAM-P characterized by a high frequency of age-associated systemic amyloidosis and not in that of senile amyloidosis-resistant SAM-R and slc:ICR mice. The nucleotide sequence analysis of cDNA clone for apo A-II of SAM-P and SAM-R confirmed that this amino acid replacement is caused by two nucleotide substitution (CCA for proline codon to CAG for glutamine codon). These results suggested that this mutation (Pro5→Gln) probably has significant effects on the structure and function of apo A-II and would play a critical role in murine senile amyloidogenesis.
KeywordsAccelerate Senescence Prone Mouse Senescence Accelerate Mouse Amyloid Fibril Protein Senile Amyloidosis Pyrrolidone Carboxylic Acid
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- 1.Higuchi, K., Matsumura, A., Hashimoto, K., Honma, A., Takeshita, S., Hosokawa, M., Yasuhira, K., and Takeda, T. 1983a, Isolation and characterization of senile amyloid-related antigenic substance (SASSAM) from mouse serum:Apo SASSAM is a low molecular weight apoprotein of high density lipoprotein., J. Exp. Med. 158:1600CrossRefGoogle Scholar
- 2.Higuchi, K., Matsumura, K., Honma, A., Takeshita, S., Hashimoto, K., Hosokawa, M., Yasuhira, K., and Takeda, T. 1983b, Systemic senile amyloid in senescence-accelerated mice:A unique fibril protein demonstrated in tissues from various organs by the unlabeled immunoperoxidase method., Lab. Invest. 48:231.Google Scholar
- 3.Higuchi, K., Matsumura, K., Honma, A., Toda, K., Takeshita, S., Matsushita, M., Yonezu, T., Hosokawa, M., and Takeda, T. 1984, Age-related changes of serum,apoprotein SASSAM, apoprotein A-I and low density lipoprotein levels in Senescence Accelerated Mouse (SAM)., Mech. Aging Dev. 26:311.CrossRefGoogle Scholar
- 4.Higuchi, K., Yonezu, T., Kogishi, K., Matsumura, A., Takeshita, S., Higuchi, K., Kohno, A., Matsushita, M., Hosokawa, M., and Takeda, T. 1986a., Purification and characterization of a senile amyloid-related antigenic substance (apo SASSAM) from mouse serum:Apo SASSAM is an apo A-II apolipoprotein of mouse high density lipoproteins., J. Biol. Chem. 261:12834Google Scholar
- 7.Hosokawa, M., Kasai, R., Higuchi, K., Takeshita, S., Shimizu, K., Honma, A., Irino, M., Toda, K., Matsumura, A., Matsushita, M., and Takeda, T. 1984., Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM). Mech. Aging Dev. 26:91.CrossRefGoogle Scholar
- 8.Kunisada, T., Higuchi, K., Aota, S., Takeda, T., and Yamagishi, H. 1986., Molecular cloning and nucleotide sequence of cDNA for murine senile amyloid protein:Nucleotide substitutions found in apolipoprotein A-II cDNA of Senescence Accelerated Mouse (SAM). Nucl. Acids Res. 14:5729.CrossRefGoogle Scholar
- 9.Marsha, N., M., and Lawrenece C. 1986., Structure and evolution of the apolipoprotein multigene family. J. Mol. Biol. 187:325.Google Scholar
- 10.Matsumura, A., Higuchi, K., Shimizu, K., Hosokawa, M., Hashimoto, K., Yasuhira, K., and Takeda, T. 1982., A novel amyloid fibril protein isolated from senescence-accelerated mice. Lab. Invest. 47:270.Google Scholar
- 14.Takeshita, S., Higuchi, K., Hosokawa, M., Matsumura, A., Higuchi, K., Kohno, A., Matsushita, M., Yonezu, T., and Takeda, T. 1985., Morphologic demonstration of cytoplasmic ASSAM-related antigenic substance (CASSAM) by an immunoperoxidase technique. Am. J, Pathol. 121:455.Google Scholar
- 16.Yonezu, T., Tsunasawa, S., Higuchi, K., Kogishi, K., Naiki, H., Hanada, K., Sakiyama, F., and Takeda, T. 1987., A molecular-pathologic approach to murine senile amyloidosis:Serum precursor-apolipoprotein A-II variant (Pro5→Gln) presents only in the senile amyloidosis-prone SAM-P/1 and SAM-P/2 mice. Lab. Invest. 57:65.Google Scholar