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Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism.

Esumi H, Sugimura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan .

ABSTRACT
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.

No MeSH data available.


Schematic representation of aberrantly spliced albumin mRNA.Albumin gene consists of 15 exons, Z,A,B,–,N, but for simplicity, only part of the mRNA structure is presented in this figure.
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f6-83_101: Schematic representation of aberrantly spliced albumin mRNA.Albumin gene consists of 15 exons, Z,A,B,–,N, but for simplicity, only part of the mRNA structure is presented in this figure.

Mentions: How was it possible to convert hepatocytes missing seven bases in an intron of albumin gene to cells able to produce albumin molecules? To answer this question, we isolated albumin mRNA from the foci of immunoreactive cells. Overcoming various daunting problems, we eventually succeeded in identifying albumin mRNA that could be translated into albumin protein with a smaller molecular weight than standard albumin. A summary of the results is schematically represented in Fig. 6. The amounts of cytoplasmic albumin mRNA in the livers of young alb−/− rats not treated with carcinogen was only trace compared to the levels in alb+/+ rats, but most cytoplasmic albumin mRNA was missing only exon H and had been formed by exon skipping between exons G and I.


Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism.

Esumi H, Sugimura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2007)

Schematic representation of aberrantly spliced albumin mRNA.Albumin gene consists of 15 exons, Z,A,B,–,N, but for simplicity, only part of the mRNA structure is presented in this figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756734&req=5

f6-83_101: Schematic representation of aberrantly spliced albumin mRNA.Albumin gene consists of 15 exons, Z,A,B,–,N, but for simplicity, only part of the mRNA structure is presented in this figure.
Mentions: How was it possible to convert hepatocytes missing seven bases in an intron of albumin gene to cells able to produce albumin molecules? To answer this question, we isolated albumin mRNA from the foci of immunoreactive cells. Overcoming various daunting problems, we eventually succeeded in identifying albumin mRNA that could be translated into albumin protein with a smaller molecular weight than standard albumin. A summary of the results is schematically represented in Fig. 6. The amounts of cytoplasmic albumin mRNA in the livers of young alb−/− rats not treated with carcinogen was only trace compared to the levels in alb+/+ rats, but most cytoplasmic albumin mRNA was missing only exon H and had been formed by exon skipping between exons G and I.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan .

ABSTRACT
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.

No MeSH data available.