Mouse Models

• Pkd1 and Pkd2 Knock out alleles in a BL/6 background(1-3)
• Pkd1v/v (knock in GPS cleavage mutant) in a BL/6 background(4)
• Pkhd1^△3-4 in a BL/6 background(5)
• Pkhd1^△67 in a BL/6 background (6)
• Pkhd1HA endogenously tagged at the C-terminal region in a BL/6 background (6)
• Pkd1 and Pkd2 conditional alleles in a BL/6 background (1-3)
• Pkd1 and Pkd2 conditional alleles with the mTmG reporter in a BL/6 background (1-3, 7)
• Pkd1 and Pkd2 conditional alleles with the ROSA reporter and tamoxifen Cre recombinase (1-3)
• Pkd1 and Pkd2 conditional alleles with the Pax8-rtTA and TetO-Cre, which allows renal tubular inactivation (1-3, 8)

Biospecimen Repository

Charge-back and fee-for-service (non-profit) will be determined upon request.

• Tissue specimens from Pkd1 null and Pkd2 null animals at E10.5, E12.5, E14.5
• Tissue specimens, blood and urine from Pkd1^cond; tamoxifen Cre, Rosa (and controls) with different progression of disease upon investigator’s request
• Tissue specimens (frozen and paraffine blocks) and plasma from Pkd1^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls and Pkd2^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls, inactivated at P10 and harvested at P15, P20 and P25
• Tissue specimens (frozen and paraffine blocks) and plasma from Pkd1^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls and Pkd2^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls, inactivated at P27 and harvested at P60, P100 and P120
• Upon Request: Tissue specimens (frozen and paraffine blocks) and plasma from Pkd1^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls and Pkd2^cond; Pax8-rtTA; Tet-O-Cre positive and negative controls, inactivated and harvested based on investigator’s request
• Fibroblast (MEFs) isolated at E12.5 from Pkd1 and Pkd2 Knock out alleles, Pkd1^v/v and Pkd1 and Pkd2 conditional alleles with or without mTmG reporter ($50/vial)

Preclinical Trials

• Preclinical trials of novel therapeutic compounds using Pkd1 and Pkd2 inducible models and Pkd1^v/v.
• Services available:
• MRI imaging
• eGFR using transdermal device
• Metabolic cages

Expertise

• Histopathology
• Model development and characterization
• Assistance with design of efficient breeding strategies
• Preclinical therapeutic trial assistance for research base members on a limited basis

References

1. Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007;13:1490-5.
2. Piontek KB, Huso DL, Grinberg A, Liu L, Bedja D, Zhao H, et al. A Functional Floxed Allele of Pkd1 that Can Be Conditionally Inactivated In Vivo. Journal of the American Society of Nephrology. 2004;15(12):3035-43.
3. Garcia-Gonzalez MA, Outeda P, Zhou Q, Zhou F, Menezes LF, Qian F, et al. Pkd1 and Pkd2 Are Required for Normal Placental Development. PLoS ONE. 2010;5(9):e12821.
4. Yu S, Hackmann K, Gao J, He X, Piontek K, García-González MA, et al. Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proceedings of the National Academy of Sciences. 2007;104(47):18688-93.
5. Garcia-Gonzalez MA, Menezes LF, Piontek KB, Kaimori J, Huso DL, Watnick T, et al. Genetic Interaction Studies Link Autosomal Dominant And Recessive Polycystic Kidney Disease In A Common Pathway. Human molecular genetics. 2007;16(16):1940-50.
6. Outeda P, Menezes L, Hartung EA, Bridges S, Zhou F, Zhu X, et al. A novel model of autosomal recessive polycystic kidney questions the role of the fibrocystin Cterminus in disease mechanism. Kidney International. 2017;92(5):1130-44.
7. Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. A global double-fluorescent Cre reporter mouse. Genesis. 2007 Sep;45(9):593-605. doi: 10.1002/dvg.20335. PMID: 17868096.
8. Traykova-Brauch M, Schönig K, Greiner O, Miloud T, Jauch A, Bode M, et al. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nature medicine. 2008;14(9):979-84.