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Published on: May 20, 2015
Selective expression of hepatocellular membrane proteins in mice homozygous for a lethal chromosomal deletion
Abstract:
Previous studies of mice homozygous for one of several overlapping radiation-induced deletions in chromosome 7 revealed reduced expression of a number of hepatocyte proteins. These proteins include the plasma membrane receptors for insulin, epidermal growth factor, and glucagon, all of which are reduced in number by over 70% with no change in apparent affinity constants. It is not known whether all or only select liver cell surface proteins are so affected in newborn deletion homozygotes. In the present study, we investigated expression of two additional, functionally distinct intrinsic hepatocellular membrane binding proteins: the hepatic binding protein (HBP: the receptor for asialoglycoproteins), and the organic anion binding protein (OABP) which may play a role in organic anion transport. Immunoblot analysis showed the content of OABP and HBP in neonatal mutants to be identical to that in controls. As compared to adults, neonates showed levels of only about 8% of HBP and 75% of OABP binding proteins. Assays of HBP binding activities confirmed these results. The normal levels of these hepatocyte binding proteins in the deletion homozygotes suggest that the DNA sequences deleted in these mutants do not regulate all genes encoding such proteins but only a selected number of them.
Insights
Radiation-induced deletions in mouse chromosome 7 affect specific liver cell surface proteins. However, hepatic binding protein (HBP) and organic anion binding protein (OABP) levels remain normal in deletion homozygotes.
Area of Science:
- Molecular Biology
- Genetics
- Hepatology
Background:
- Radiation-induced deletions in mouse chromosome 7 have been linked to reduced expression of several hepatocyte proteins, including key plasma membrane receptors.
- The impact of these deletions on all liver cell surface proteins, particularly in neonates, remains unclear.
Purpose of the Study:
- To investigate the expression of two distinct intrinsic hepatocellular membrane binding proteins: hepatic binding protein (HBP) and organic anion binding protein (OABP) in neonatal deletion homozygotes.
- To determine if the deleted DNA sequences regulate all genes encoding hepatocyte binding proteins or only a select subset.
Main Methods:
- Immunoblot analysis was used to quantify the content of OABP and HBP in neonatal mutant mice compared to controls.
- Binding activity assays for HBP were performed to confirm expression levels.
Main Results:
- Immunoblot analysis revealed normal levels of OABP and HBP in neonatal deletion homozygotes, identical to control littermates.
- Neonatal mice, in general, exhibited lower levels of HBP (approx. 8%) and OABP (approx. 75%) compared to adult levels.
- HBP binding activity assays corroborated the immunoblot findings.
Conclusions:
- The findings suggest that the deleted DNA sequences in chromosome 7 do not globally affect all genes for hepatocyte binding proteins.
- Only a selected number of genes encoding liver cell surface proteins are regulated by the deleted region, as evidenced by the normal expression of HBP and OABP.
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