- Email: [email protected]
Ultrastructural study of non-diabetic lesions in mice used in experimental diabetes
ULTRASTRUCTURAL STUDYOF NON-DIABETIC LESIONS IN MICE USED IN EXPERIMENTALDIABETES Manuel G. Soret, T i l l i e Peterson and Edward M. Block Department of Pathology and Toxicology Research The Upjohn Company, Kalamazoo, MI 49001
Spontaneously diabetic animals are very useful in diabetes research. One of these experimental models, the KK mouse, has been widely used since the original work of Kondo (1957) and Nakamura (1967). Renal lesions from this strain of mice have been described as resembling the glomerulosclerosis associated with human diabetes based on the increased deposition of PAS+material in the mesangial matrix of the glomerulus (Soret, e>t a~., in press). Similar lesions were observed in phenotypically lean KK mice (Figure I). However, these lean KK mice were neither glucosuric nor hyperglycemic. Furthermore, the lean KK mic~ had perifollicular deposition of hyaline material in the spleen as well as heavy i n f i l t r a t i o n of the hepatic sinusoid by a similar hyaline substance. This evidence made i t d i f f i c u l t to relate the glomerulosclerosis observed in lean KK mice to diabetes. Additional histochemical tests suggested that the hyaline material was amyloid. Congo Red Staining using fluorescence microscopy strongly suggested the presence of amyloid in the mesangial matrix of the glomerulus (Figure 2). Confirmation of amyloid was made at the ultrastructure level (Figure 3). The typical amyloid f i b r i l s are straight, about 12.5-16.0 nm wide, not branching and randomly arranged.
Kondo K, Nozawa K, Tomida T, Ezaki K, 1957. Bull. Exp. Animals, 6, 107. Nakumura M and Yamada K, 1967. Diabetologia, 3, 212. Soret MG, Peterson T, Wyse B, Block EM, Dulin WE, Arch. Pathol. Lab. Med., in press.
179
180
M . G . Soret, T. Peterson and E. M. Block
Figures I - 3 . Nondiabetic renal lesions in KK mice. Fig. I. Mesangial enlargement. PAS; o r i g i n a l magnification x360. Marker = I0 ~m. Fig. 2. Green fluorescence of mesangial deposits. Congo Red; o r i g i n a l magnification x360. Marker = lO ~m. Fig. 3. Amyloid deposition in the mesangium. Uranyl acetatelead c i t r a t e ; o r i g i n a l magnification x45,360. Marker = 0.1 ~m.
Spontaneously diabetic animals are very useful in diabetes research. One of these experimental models, the KK mouse, has been widely used since the original work of Kondo (1957) and Nakamura (1967). Renal lesions from this strain of mice have been described as resembling the glomerulosclerosis associated with human diabetes based on the increased deposition of PAS+material in the mesangial matrix of the glomerulus (Soret, e>t a~., in press). Similar lesions were observed in phenotypically lean KK mice (Figure I). However, these lean KK mice were neither glucosuric nor hyperglycemic. Furthermore, the lean KK mic~ had perifollicular deposition of hyaline material in the spleen as well as heavy i n f i l t r a t i o n of the hepatic sinusoid by a similar hyaline substance. This evidence made i t d i f f i c u l t to relate the glomerulosclerosis observed in lean KK mice to diabetes. Additional histochemical tests suggested that the hyaline material was amyloid. Congo Red Staining using fluorescence microscopy strongly suggested the presence of amyloid in the mesangial matrix of the glomerulus (Figure 2). Confirmation of amyloid was made at the ultrastructure level (Figure 3). The typical amyloid f i b r i l s are straight, about 12.5-16.0 nm wide, not branching and randomly arranged.
Kondo K, Nozawa K, Tomida T, Ezaki K, 1957. Bull. Exp. Animals, 6, 107. Nakumura M and Yamada K, 1967. Diabetologia, 3, 212. Soret MG, Peterson T, Wyse B, Block EM, Dulin WE, Arch. Pathol. Lab. Med., in press.
179
180
M . G . Soret, T. Peterson and E. M. Block
Figures I - 3 . Nondiabetic renal lesions in KK mice. Fig. I. Mesangial enlargement. PAS; o r i g i n a l magnification x360. Marker = I0 ~m. Fig. 2. Green fluorescence of mesangial deposits. Congo Red; o r i g i n a l magnification x360. Marker = lO ~m. Fig. 3. Amyloid deposition in the mesangium. Uranyl acetatelead c i t r a t e ; o r i g i n a l magnification x45,360. Marker = 0.1 ~m.