Sense and antisense transcripts of the apolipoprotein E gene in normal and ApoE knockout mice, their expression after spinal cord injury and corresponding human transcripts
Autor: | Stefan J. Samulewicz, Natasha Levenkova, Ellen Heber-Katz, Xiang-Ming Zhang, John J. Rux, Alexander Seitz, Dmitri Gourevitch, Lise Clark, Maja Kragol, Pan Chen |
---|---|
Rok vydání: | 2005 |
Předmět: |
Apolipoprotein E
Blotting Western Molecular Sequence Data Biology Mice Exon Apolipoproteins E Sense (molecular biology) Gene expression Genetics Animals Humans RNA Antisense RNA Messenger Molecular Biology Spinal Cord Injuries Genetics (clinical) DNA Primers Mice Knockout Base Sequence Reverse Transcriptase Polymerase Chain Reaction General Medicine Blotting Northern Null allele Molecular biology Antisense RNA Mice Inbred C57BL Gene Expression Regulation Sense strand Knockout mouse lipids (amino acids peptides and proteins) |
Zdroj: | Human Molecular Genetics. 14:2661-2670 |
ISSN: | 1460-2083 0964-6906 |
Popis: | The apolipoprotein E (ApoE) gene has been linked to maladies such as hypercholesterolemia, CNS injury and disease. In this study, we present evidence that, in addition to the known transcript (ApoE S1) that translates into ApoE, there are three additional transcripts in mice. Two of these transcripts, ApoE S2 and ApoE S3, which are predicted to be transmembrane proteins, are transcribed from the sense strand. ApoE AS1 is transcribed from the antisense strand and is complementary to exon 4 of ApoE S1. The open reading frame of ApoE AS1 is conserved between human and mouse. The antisense transcript falls within the region of the human epsilon 4 allele that has been linked to the familial onset form of Alzheimer's disease. We also demonstrate the expression of ApoE S3 and ApoE AS1 in ApoE knockout mice, and ApoE S1 and ApoE S2 do not get transcribed. We had previously identified ApoE S1 as being upregulated in mice after spinal cord injury. In this study, we show that in spinal cord-injured C57BL/6 mice, both ApoE S1 and ApoE S3 transcripts are 10-fold upregulated and the antisense ApoE AS1 is 100-fold upregulated compared with normal levels. Such data suggest that these alternate transcripts are involved in the molecular pathogenesis of CNS disease and perhaps in ApoE expression in general, as we show that ApoE S2 and AS1 are also transcribed in human. |
Databáze: | OpenAIRE |
Externí odkaz: |