Podocyte cell-specific expression of doxycycline inducible Cre recombinase in mice.
Conventional silencing of many podocyte-specific genes in mice is associated with embryonic or perinatal lethality. Therefore, it would be of great importance to generate mouse models that allow the modification of genes that are expressed in podocytes at later stages of age. Herein is described a transgenic mouse with doxycycline-inducible podocyte-specific expression of Cre recombinase. For the generation of this binary system, a single transgenic construct that contained two separate genes was used: One encoding the optimized M2 version of the doxycycline-dependent transcription transactivator reverse tetracycline-controlled transcriptional activator (rtTA) under control of the human podocin (NPHS2) promoter and the other encoding the recombinase Cre under control of the rtTA/doxycycline-responsive minimal cytomegalovirus (CMV) Tet operator sequence 7 promotor. Microinjection of the JRC-CRE construct in fertilized oocytes from FVB/N mice resulted in 16 transgenic founders. Double-transgenic offspring from breeding of a selected founder with the Z/AP reporter mouse showed alkaline phosphatase staining only upon doxycycline administration and exclusively in podocytes. These data indicate that this new inducible Cre recombinase mouse line is an excellent tool in conditional, kidney glomerular podocyte-specific gene deletion in adult mice.
Juhila
Juuso
J
Research Program in Molecular Medicine, Biomedicum, University of Helsinki, Helsinki, FI-00014 Finland.
Roozendaal
Ramon
R
Lassila
Markus
M
Verbeek
Sjef J
SJ
Holthofer
Harry
H
D000818:Animals; D004318:Doxycycline / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D019426:Integrases / Q000235:genetics* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D004318:Doxycycline