Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism

Serum albumin is regarded as an important and indispensable protein, but analbuminemic rats established by Sumi Nagase in 1977 seems to exhibit few symptoms in spite of an almost total lack of albumin in the serum. The albumin gene of analbuminemic rats was found to have a seven-base-pair deletion in an intron, close to exon-intron junction, resulting in the formation of non-functional mRNA in hepatocytes. Immunostaining for albumin was negative in young analbuminemic rat hepatocytes, but a significant number of immunoreactive hepatocytes were observed in aged rats. The incidence of immunoreactive hepatocytes increased with aging. Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters. Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping. The altered albumin molecules thus synthesized accumulated in cellular organelles. Analbuminemic rats exhibited a high sensitivity in various organs to different types of carcinogens. Further challenges remain regarding the biology of analbuminemic rats.