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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.


Related in: MedlinePlus

Albumin transcription and serum AFP concentrations.a. Time dependent change of serum AFP (•) and serum albumin (○) concentration after birth in alb+/+ and alb−/− rats.b. Time dependent change of serum AFP concentration (○) and amount of albumin gene transcript (•) in the nuclei of the liver of alb+/+ and alb−/− rats.The serum AFP concentration was measured by a single radial immunodiffusion method using a specific antibody against AFP. RNA was extracted from rat liver nuclei and quantitated by a method involving RNA-cDNA hybridization followed by S1 nuclease digestion (Modified from Cancer Res. 42, 306–308 (1982)).6)
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f3-83_101: Albumin transcription and serum AFP concentrations.a. Time dependent change of serum AFP (•) and serum albumin (○) concentration after birth in alb+/+ and alb−/− rats.b. Time dependent change of serum AFP concentration (○) and amount of albumin gene transcript (•) in the nuclei of the liver of alb+/+ and alb−/− rats.The serum AFP concentration was measured by a single radial immunodiffusion method using a specific antibody against AFP. RNA was extracted from rat liver nuclei and quantitated by a method involving RNA-cDNA hybridization followed by S1 nuclease digestion (Modified from Cancer Res. 42, 306–308 (1982)).6)

Mentions: It is well known that α-fetoprotein is synthesized in the embryonic liver and replaced by albumin 2–3 weeks after the birth. As expected, in alb+/+ control rats, serum α-fetoprotein concentrations reached a maximum just after birth, about 10 mg/ml, and gradually decreased to almost undetectable level at 4 weeks thereafter, with concomitant increase of serum albumin concentration. In analbuminemic rats (alb−/−), changes of serum α-fetoprotein concentrations mirrored those in normal rats, but the serum albumin concentration did not increase after birth at all, suggesting that shut-off of α-fetoprotein gene transcription took place despite the lack of albumin increase (Fig. 3a). Consistent with these findings, immature mRNA for albumin began to appear from 1 week after birth and increased further during the following a few weeks as in the normal rat (alb+/+) liver (Fig. 3b). This phenomenon indicated that the switch-on and -off mechanisms for α-fetoprotein and albumin occurred at the gene-transcription level.6)


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

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

Albumin transcription and serum AFP concentrations.a. Time dependent change of serum AFP (•) and serum albumin (○) concentration after birth in alb+/+ and alb−/− rats.b. Time dependent change of serum AFP concentration (○) and amount of albumin gene transcript (•) in the nuclei of the liver of alb+/+ and alb−/− rats.The serum AFP concentration was measured by a single radial immunodiffusion method using a specific antibody against AFP. RNA was extracted from rat liver nuclei and quantitated by a method involving RNA-cDNA hybridization followed by S1 nuclease digestion (Modified from Cancer Res. 42, 306–308 (1982)).6)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-83_101: Albumin transcription and serum AFP concentrations.a. Time dependent change of serum AFP (•) and serum albumin (○) concentration after birth in alb+/+ and alb−/− rats.b. Time dependent change of serum AFP concentration (○) and amount of albumin gene transcript (•) in the nuclei of the liver of alb+/+ and alb−/− rats.The serum AFP concentration was measured by a single radial immunodiffusion method using a specific antibody against AFP. RNA was extracted from rat liver nuclei and quantitated by a method involving RNA-cDNA hybridization followed by S1 nuclease digestion (Modified from Cancer Res. 42, 306–308 (1982)).6)
Mentions: It is well known that α-fetoprotein is synthesized in the embryonic liver and replaced by albumin 2–3 weeks after the birth. As expected, in alb+/+ control rats, serum α-fetoprotein concentrations reached a maximum just after birth, about 10 mg/ml, and gradually decreased to almost undetectable level at 4 weeks thereafter, with concomitant increase of serum albumin concentration. In analbuminemic rats (alb−/−), changes of serum α-fetoprotein concentrations mirrored those in normal rats, but the serum albumin concentration did not increase after birth at all, suggesting that shut-off of α-fetoprotein gene transcription took place despite the lack of albumin increase (Fig. 3a). Consistent with these findings, immature mRNA for albumin began to appear from 1 week after birth and increased further during the following a few weeks as in the normal rat (alb+/+) liver (Fig. 3b). This phenomenon indicated that the switch-on and -off mechanisms for α-fetoprotein and albumin occurred at the gene-transcription level.6)

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.


Related in: MedlinePlus