SUBNORMAL ALBUMIN GENE-EXPRESSION IS ASSOCIATED WITH WEIGHT-LOSS IN IMMUNODEFICIENT DNA-REPAIR-IMPAIRED WASTED MICE

Objective: Mice bearing the autosomal recessive mutation wst express a disease syndrome of immunodeficiency, neurologic dysfunction, increas ed sensitivity to the killing effects of ionizing radiation, and drama tic weight loss that begins at 21 days of age and progresses until dea th at 28-32 days of age. Because of the reported association between a bnormal liver status and weight loss, we designed experiments to exami ne expression of a variety of liver-specific genes in wst/wst mice rel ative to littermates (wst/.) and parental strain (BCF1) controls. Meth od: Animals were individually weighed from ages 21-28 days to determin e relative weight comparisons between wst/wst mice and controls. Dot b lot hybridizations were set up to quantitate the accumulation of trans cripts specific for alpha-fetoprotein, albumin and other liver-specifi c gene products. Results: These results showed a 67% reduction in albu min mRNA expression in livers derived from wst/wst mice relative to bo th controls. Expression of a-fetoprotein, as well as a variety of othe r liver-specific genes [secretory component (SC), metallothionein (MT- 2), cytochrome P1-450 (Cyt P1-450), transferrin receptor (Tf Rec), tum or necrosis factor (TNF), and immune-associated antigen (1a)], was una ffected. Conclusions: These results suggest a relationship between low albumin expression and wasting syndromes in mice. In addition, our da ta suggest that the wasted mouse may serve as a unique model for subno rmal albumin expression.