The objective of this core is to facilitate the use of mouse models to study Polycystic Kidney Disease.

Mouse models

Charge-back (non-profit) ($125 per animal)

• Pkd1 and Pkd2 Knock out alleles in a BL/6 background^(1-3).
• Pkd1^v/v (knock in GPS cleavage mutant) in a BL/6 background⁽⁴⁾.
• Pkhd1^del3-4 in a BL/6 background⁽⁵⁾.
• Pkhd1^67 in a BL/6 background ⁽⁶⁾.
• Pkhd1HA endogenously tagged in 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 a reporter and tamoxifen Cre recombinase^(1-3).
• Pkd1 and Pkd2 conditional alleles with Pax8-rtTA and TetO-Cre which allows renal tubular inactivation⁽⁶⁾.
• Conditional alleles with other Cre recombinase lines available on request.

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/cond; tamoxifen Cre, Rosa (and controls) induced at P21²
• Specimens collected monthly post induction, correlated with MRI
• Samples available from additional models upon request
• Fibroblast (MEFs) isolated at E12.5 from Pkd1 and Pkd2 Knock out alleles, Pkd1^v/v and Pkd1 and Pkd2 conditional alleles ($50/vial).

Preclinical Trials

Fee-for-service will be determined upon request

• Preclinical trials of novel therapeutic compounds using Pkd1 and Pkd2 inducible models and Pkd1^v/v
• MRI imaging available
• Models Available to Perform Preclinical Trials.

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 C-terminus in disease mechanism. Kidney International. 2017;92(5):1130-44.
7. 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.
8. Shao X; Somlo S; Igarashi P. 2002. Epithelial-specific Cre/lox recombination in the developing kidney and genitourinary tract. J Am Soc Nephrol 13(7):1837-46