CHARACTERIZATION OF TRANSGENIC MICE LINEAGES .1. OVEREXPRESSION OF HGH CAUSES THE FORMATION OF LIVER INTRANUCLEAR PSEUDOINCLUSION BODIES AND RENAL AND HEPATIC-INJURY

The expression of the human Growth Hormone (hGH) in transgenic mice is accompanied by health afflictions and structural changes in several organs and tissues. A macroscopic and light microscopic study was conducted to examine the morphological alterations related to the exposure of endogenously expressed hGH. Although many transgenic mice were under cachectic status, their body and organ weights were significantly higher than those of the controls matched. Kidney, liver and female genital organs were massively damaged. The most common findings in these organs were glomeruli hyalinosis and glomerulosclerosis in the kidneys accompanied by a varying degree of segmental sclerosis and necrosis. Tubuli dilatation was observed with hyaline casts and atrophied epithelium as well as interstitial fibrosis with mononuclear infiltrate. In the liver the hepatocytes were pleomorphic and exhibited vacuolar degeneration. Intranuclear lipid droplets were also found. Individual necrosis, mononuclear infiltrate and nuclear pseudoinclusions were also detected. The uterus exhibited cystic glandular hyperplasia and ovaries were observed to have several, large foamy cells as well as stromal infiltration of adipose cells. Other changes were found in the heart, the spleen and the salivary glands. A possible role of GH and/or the Insulin-like Growth Factor-I is suggested according to the morphological changes found. The similarity to kidney changes with human diabetic glomerulosclerosis was noticed.