Chemical and immunological studies of liver microsomes from mouse mutants with ultrastructurally abnormal hepatic endoplasmic reticulum

Abstract

Investigations of the lethal effects of a series of radiation-induced deletion alleles in the mouse have identified severe ultrastructural abnormalities of endoplasmic reticulum liver membranes in lethal albino homozygous newborns. The ultra-structural defects were accompanied by deficiencies of several enzymes, some of them microsomal membrane bound. Chemical and immunological studies were therefore undertaken in order to identify a possible biochemical alteration of mutant endoplasmic reticulum membranes. Patterns of gel electrophoresis produced by several different methods showed no differences between the microsomal proteins of mutant and normal mice. Immunological methods also failed to detect any changes in the major proteins. Thus in spite of the severe ultrastructural defects no major differences between microsomal proteins of mutant and normal membranes could be identified. Since several of the enzymes affected are inducible by cAMP in newborn mice, microsomal and supernatant cAMP-binding activities were also measured in mutants and normals but showed no differences. As yet, the primary cause of the severe effects of the X-ray-induced deletions on membrane structure and enzyme activities remains unknown.