Mdr1a Knockout Rat
Nomenclature:
SD-
Abcb1a
tm1sage
Genotype:
Homozygous
Product number:
TGRS3570
Description
This model contains a bi-allelic deletion of 20 base pairs within exon 7 of the multi-drug resistance gene Mdr1a, synonym Abcb1a (ATP-binding cassette, sub-family B [MDR/TAP], member 1A), encoding P-glycoprotein 3. The deletion causes a frameshift in the coding region, resulting in a premature termination codon at the end of exon 7.
Additional Information
P-glycoprotein is a membrane-bound drug transporter expressed in the brain and intestine. It effectively blocks drugs from crossing the blood-brain barrier. P-gp can confer multiple drug resistance to tumor cells. Absence of P-gp creates a functional deficiency in the blood-brain barrier and results in elevated drug levels in many tissues, making this a useful model for studying neurotoxicology, drug transport and chemotherapeutic agents.
Additional DataLine 437, 20bp deletion
Wildtype--End of exon 7, ZFN design in red:
5’- TCTTGTGATTTTGGCCATCAGCCCTGTTCTTGGACTGTCAGCTGGTATTTGGGCAAAG
Exon 7 ends at G
20 bp deletion (blue) in F1 GT:
5’- TCTTGTGATTTTGGCCATCAGCCCTGTTCTTGGACTGTCAGCTGGTATTTGGGCAAAG
RT-PCR data-- cDNA transcript- ileum and brain:
5’- TCTTGTGATTTTGGCCATCAGCCCTGTTCTTGGACTGTCAGCTGGTATTTGGGCAAAG
5’- TCTTGTGATTTTGGCCATCAGCTGGTATTTGGGCAAAGATATTGTCTTCATTTACTGA
TGA = Stop
Characteristics
- Total loss of P-glycoprotein protein via western blot
- Accumulation of substrate drugs in the brain
- Decreased drug elimination
- Susceptible to irritable bowel disease (IBD)
- Albino
Research Applications
- PK/PD studies
- Neurotoxicology
- Drug transport
- Dosing/Bioavailablity studies
- Drug resistance studies