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Reye’s-Like Syndrome

Reye's-like syndrome, an important cause of morbidity and mortality among human infants and children, is characterized as hepatoencephalopathy and fatty degen­eration of viscera.

Antecedent viral infections and aspi­rin therapy are precipitating factors in humans. Outbreaks of Reye's-like syndrome, although rare, occur with high morbidity and mortality. The natural disease has been principally associated with BALB/cByJ mice, but similar findings have been reported in infant C3H-H- 2o mice. Precipitating factors have not been defined but may be linked to enterotropic MHV or other infections. Experimental infection of C.B-17-scid mice with mouse adenovirus (MAdV-1) can induce the syndrome. Reye's- like syndrome in mice, as in humans, is characterized by a rapidly deteriorating encephalopathy secondary to hepatic dysfunction with hyperammonemia. The meta­bolic defect is unknown, but mitochondrial swelling with dysfunction in hepatocytes is the primary lesion. Affected mice become precipitously stuporous and comatose with hyperventilation. Death occurs in most cases within 6-18 hours after onset, but some mice regain consciousness.

Livers are swollen, greasy, and pale, and kidneys are swollen, with pale cortices. Intestines can be fluid- and gas-filled, with empty ceca. Microscopic findings include marked microvesicular fatty change and swell­ing of hepatocytes, with sinusoidal hypoperfusion (Fig. 1.107). Ultrastructural changes include disruption of mitochondrial cristae and cytoplasmic vacuolation filled with lipid. Moderate numbers of fat vacuoles are also present in renal proximal convoluted tubular epi­thelium. Neurologic lesions consist of swelling of pro­toplasmic astrocyte nuclei (Alzheimer type II astrocytes) in the neocortex, corpus striatum, hippo­campus, and thalamus. The hepatic pathology must be differentiated from hepatocellular fatty change that is common in BALB/c mice, which normally possess a moderate degree of this change.

Graft Versus Host Diseases

Although graft versus host disease (GVHD) is not a naturally occurring syndrome in laboratory mice, the mouse has been used extensively to study various ele­ments of acute and chronic GVHD, and the reader is referred to recent reviews (Anderson & Bluestone 2005; Schroeder & DiPersio 2011). GVHD has become impor­tant with xenotransplantation of human stem cell and T cells into NOD/SCID, NSG and other immunodeficient mice, so mouse pathologists are often involved in exam­ining such mice. Acute GVHD is primarily mediated through the CD8+ T-cell alloreactivity, resulting in acute disease with infiltration of lymphocytes into skin, liver, intestine, lungs, and kidneys. Chronic GVHD is primar­ily mediated through CD4+ T-cell alloreactivity, with B- cell expansion, lymphadenopathy, splenomegaly, bili­ary damage, scleroderma, and autoantibody production, resulting in glomerulonephritis.

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Source: Barthold Stephen W., Griffey Stephen M., Percy Dean H.. Pathology of Laboratory Rodents and Rabbits. 4th Edition. — Wiley-Blackwell,2016. — 384 p.. 2016
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