Mechanisms of salt and water homeostasis in the kidney




1 ECTS (participation at both sessions)
0.25 ECTS (participation in the morning)

When :

FRIDAY, December 10, 2010
09.00am - 16:30pm


Auditorium Charlotte Olivier
Rue du Bugnon 21
1011 Lausanne


Faculty/Staff - Student

Professor Olivier Staub


Online registration:



Johannes Loffing

 Mechanisms of cation transport along the nephron

Zurich Switzerland

Kevin O'Shaughnessy

Unravelling the molecular genetics of Gordon Syndrom


Udo Hasler

Mechanisms controlling aquaporin-2 expression and subcellular repartition


Michael Caplan

Role of olfactory receptors in the nephron





Mechanisms of cation transport along the nephron
Johannes Loffing, Zurich, Switzerland

In this talk the physiology of the kidney will be discussed, based on data derived from mouse models. The morphology and the function of the various nephron segments will be presented, based on data derived primarily from mice and rats. Regulatory mechanisms of cation homeostasis are presented by citing numerous transgenic and KO models, and experimental approaches with mice discussed.


Unravelling the molecular genetics of Gordon Syndrome
Kevin O'Shaugnessy, Cambridge, UK

Gordon syndrome, a kidney disease causing hypertension and hyperkalemia, will be discussed, both with respect to its pathology, genetics and molecular mechanisms. Several transgenic mouse lines will be presented, and a novel SPAK knock-in mouse discussed. Techniques involve the generation of the mouse models, measurements of arterial blood pressure on the animal, and measuring various renal parameters by sampling urine and blood.


Regulation of water transport in the nephron
Soren Nielsen, Aarhus, Danmark

In this talk, the in vivo regulation of water homeostasis is discussed by evaluating primarily different mice models. Acute AP2 regulation will be approached by immunohistochemistry, measurements of renal parameters, and various experimental interventions (application of vasopressin, lithium, salt diets). A proteasomal approach on mouse kidneys will also be presented.


Role of olfactory receptors in the nephron
Michael Caplan, Yale, USA

Michael Caplan’s laboratory identified recently a number of olfactory receptors, olfactory adenylate cyclise 3 (AC3) and olfactory G-protein (Golf) that are co-expressed in the kidney tubules and in the Macula densa, which regulates glomerular filtration rate (GFR). The effect of knockout of AC3 in mice on the GFR and on the regulation of renin expression will be discussed.

In the afternoon:

Various papers have been proposed to the students, and will be discussed in the afternoon with the speakers (see list of papers here below).

They all contain mouse models, detailed description how to analyze renal parameters in the mouse (ion homeostasis, blood pressure, immunohistochemistry).


We therefore asked that students participating in the afternoon session will get additional accreditation.



The following papers will be discussed:

Proposed by J. Loffing:
Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann KE, Toka HR, Nelson-Williams C, Ellison DH, Flavell R, Booth CJ, Lu Y, Geller DS, Lifton RP. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006 Oct;38(10):1124-32
Frindt G, Palmer LG. Effects of dietary K on cell-surface expression of renal ion channels and transporters. Am J Physiol Renal Physiol. 2010 Oct;299(4):F890-7

Proposed by K. O'Shaugnessy:
Hadchouel J, Soukaseum C, Büsst C, Zhou XO, Baudrie V, Zürrer T, Cambillau M, Elghozi JL, Lifton RP, Loffing J, Jeunemaitre X. Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18109-14
Yang SS, Lo YF, Wu CC, Lin SW, Yeh CJ, Chu P, Sytwu HK, Uchida S, Sasaki S, Lin SH. SPAK-Knockout Mice Manifest Gitelman Syndrome and Impaired Vasoconstriction. J Am Soc Nephrol. 2010 Nov;21(11):1868-77

Discussed with Udo Hasler but proposed by S. Nielsen:
Fenton RA, Moeller HB, Hoffert JD, Yu MJ, Nielsen S, Knepper MA. Acute regulation of aquaporin-2 phosphorylation at Ser-264 by vasopressin. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3134-9
Nielsen J, Hoffert JD, Knepper MA, Agre P, Nielsen S, Fenton RA. Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: mechanisms for aquaporin 2 down-regulation and cellular proliferation. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3634-9

Proposed by M. Caplan:
Farr GA, Hull M, Mellman I, Caplan MJ. Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells. J Cell Biol. 2009 Jul 27;186(2):269-82
Pluznick JL, Zou DJ, Zhang X, Yan Q, Rodriguez-Gil DJ, Eisner C, Wells E, Greer CA, Wang T, Firestein S, Schnermann J, Caplan MJ. Functional expression of the olfactory signaling system in the kidney. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2059-64

Université de Lausanne Centre Hospitalier Universitaire Vaudois (CHUV)