| First Author | Pippert TR | Year | 2001 |
| Journal | J Biochem Mol Toxicol | Volume | 15 |
| Issue | 2 | Pages | 83-9 |
| PubMed ID | 11284049 | Mgi Jnum | J:253168 |
| Mgi Id | MGI:6108655 | Doi | 10.1002/jbt.3 |
| Citation | Pippert TR, et al. (2001) The subpopulation of CF-1 mice deficient in P-glycoprotein contains a murine retroviral insertion in the mdr1a gene. J Biochem Mol Toxicol 15(2):83-9 |
| abstractText | A subpopulation of the CF-1 mouse strain is sensitive to neurotoxicity following exposure to avermectins, a family of structurally related antiparasitic agents. This unusual sensitivity is the result of a deficiency in the mdr1a P-glycoprotein that normally contributes to a functional blood-brain barrier. Previous studies demonstrated a correlation between P-glycoprotein levels in the brain, intestine, testis, and placenta with an restriction fragment length polymorphism (RFLP) pattern from DNA isolated from the animals. We have demonstrated that only P-glycoprotein derived from the mdr1a gene is deficient in these mice. In this article, we describe the genetic defect in the subpopulation of CF-1 mice resulting in an absence of P-glycoprotein. The data presented describes a reverse transcription--polymerase chain reaction (RT-PCR) protocol that specifically amplifies mdr1a mRNA from tissue and confirms that the P-glycoprotein defect results from a truncated mRNA with a deleted exon 23. Genomic amplification and sequencing of the intron between exon 22 and 23 in Pgp-deficient animals reveals an insertion of approximately 8.35 kb of DNA at the exon 23 intron--exon junction corresponding to a murine leukemia virus. This insertion results in the aberrant splicing of the mRNA and the loss of exon 23 during RNA processing. |
