Prnp knockdown in transgenic mice using RNA interference.
RNA interference has become a widely used approach to perform gene knockdown experiments in cell cultures and more recently transgenic animals. A designed miRNA targeting the prion protein mRNA was built and expressed using the human PRNP promoter. Its efficiency was confirmed in transfected cells and it was used to generate several transgenic mouse lines. Although expressed at low levels, it was found to downregulate the endogenous mouse Prnp gene expression to an extent that appears to be directly related with the transgene expression level and that could reach up to 80% inhibition. This result highlights the potential and limitations of the RNA interference approach when applied to disease resistance.
Gallozzi
Micaela
M
UR 339, Laboratoire de Génétique Biochimique et de Cytogénétique, Institut National de la Recherche Agronomique, 78350, Jouy-en-Josas, France.
Chapuis
Jérome
J
Le Provost
Fabienne
F
Le Dur
Annick
A
Morgenthaler
Caroline
C
Peyre
Coralie
C
Daniel-Carlier
Nathalie
N
Pailhoux
Eric
E
Vilotte
Marthe
M
Passet
Bruno
B
Herzog
Laetitia
L
Beringue
Vincent
V
Costa
José
J
Tixador
Philippe
P
Tilly
Gaëlle
G
Laude
Hubert
H
Vilotte
Jean-Luc
JL
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015536:Down-Regulation; D005822:Genetic Vectors; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D018621:PrPC Proteins / Q000235:genetics; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D034622:RNA Interference
D017931:DNA Primers; D035683:MicroRNAs; C512656:PRNP protein, human; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions