A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme.
Conditional gene targeting in mice has provided great insight into the role of gene function in kidney development and disease. Although a number of Cre-driver mouse strains already exist for the kidney, development of additional strains with unique expression patterns is needed. Here we report the generation and validation of a Tcf21/Pod1-Cre driver strain that expresses Cre recombinase throughout the condensing and stromal mesenchyme of developing kidneys and in their derivatives including epithelial components of the nephron and interstitial cells. To test the efficiency of this line, we crossed it to mice transgenic for either loss or gain of function β-catenin conditional alleles. Mice with deletion of β-catenin from Tcf21-expressing cells are born with hypoplastic kidneys, hydroureters and hydronephrosis. By contrast, Tcf21-Cre driven gain of function for β-catenin in mice results in fused midline kidneys and hypoplastic kidneys. Finally, we report the first renal mesenchymal deletion of Patched1 (Ptch1), the receptor for sonic hedgehog (Shh), which results in renal cysts demonstrating a functional role of Shh signaling pathway in renal cystogensis. In summary, we report the generation and validation of a new Cre driver strain that provides robust excision in metanephric mesenchyme.
The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Yoshiro
Y
Maezawa
Matthew
M
Binnie
Chengjin
C
Li
Paul
P
Thorner
Chi-Chung
CC
Hui
Benjamin
B
Alman
Makoto Mark
MM
Taketo
Susan E
SE
Quaggin
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001947:Breeding; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D023061:Gene Order; D018390:Gene Targeting; D005822:Genetic Vectors; D019426:Integrases / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D019426:Integrases; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D051176:beta Catenin; C000606240:Ptch1 protein, mouse; C112923:Tcf21 protein, mouse; C045073:Cre recombinase