Needle-shaped amyloid deposition in rat mammary gland: evidence of a novel amyloid fibril protein

Abstract

Amyloidosis is an extremely rare event in rats. In this study, we report that lipopolysaccharide binding protein (LBP) is the most likely amyloidogenic protein in rat mammary amyloidosis. Histologically, corpora amylacea (CA) and stromal amyloid (SA) were observed in rat mammary glands, and needle-shaped amyloid (NA) was also observed on the surface or gap of CA and SA. Following surveillance in aged rats, NA was observed in 62% of mammary tumours, 25% of male mammary glands and 83% of female mammary glands. Proteomic analysis showed that lactadherin was a major constitutive protein of CA and SA, and both were positive following immunohistochemistry with anti-lactadherin antibodies. In the same analysis, LBP was detected as a prime candidate protein in NA, and NA was positive following immunohistochemistry and immunoelectron microscopy with anti-LBP antibody. Furthermore, synthetic peptides derived from rat LBP formed amyloid fibrils in vitro. Overall, these results provide evidence that LBP is an amyloid precursor protein of NA in rat mammary glands.

Keywords:

• Amyloidosis
• lipopolysaccharide binding protein
• mammary gland
• pathology
• rat

Acknowledgements

The authors thank Mr. H. Watanabe for excellent technical support. The authors are greatly indebted to Prof. Jinko Sawashita (Shinshu University), Prof. Yosuke Fukutani and Prof. Masafumi Yohoda (Tokyo University of Agriculture and Technology) for technical assistance with the ThT binding assay. The authors also greatly appreciate the helpful suggestions and comments from Prof. Keiichi Higuchi (Shinshu University) and Prof. Junichi Kamiie (Azabu University).

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This research was partially supported by JSPS KAKENHI (Grant Numbers 16H05027 and 17K17702) and TUAT President’s Discretionary Funding to support the launch of next-generation research project.