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Gene Review

Rapgef5  -  Rap guanine nucleotide exchange factor...

Mus musculus

Synonyms: 4932413M22, C86120, D030051B22Rik, GFR, Gfr, ...
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Disease relevance of Rapgef5

  • Such responsiveness may contribute to reduced RBF and GFR during endotoxemia [1].
  • Whether maintained renal vascular reactivity to vasoconstrictors contributes to the decrease in renal blood flow (RBF) and GFR observed during LPS-induced sepsis was tested by assessment of the acute effects of pressor agents on mean arterial pressure (MAP) and renal hemodynamics in endotoxemic and control mice [1].
  • There were no significant differences in final body weight, urine volume and osmolality, GFR, proteinuria, or plasma levels of protein and urea between these two groups [2].
  • Sepsis-associated acute renal failure is characterized by decreased GFR and tubular dysfunction [3].
  • Eventually, with disease progression, compensating hemodynamic and structural factors fail to maintain GFR within normal limits [4].

High impact information on Rapgef5

  • In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR [5].
  • The Gfr alpha3-/- mice exhibited severe defects in the superior cervical ganglion (SCG), whereas other ganglia appeared normal [6].
  • GFR alpha2-expressing cells in the trigeminal and dorsal root ganglia are also depleted in NTN-/- mice [7].
  • Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor [8].
  • These results suggest that while stringent physiologic pairing exists between GFR alpha1 and GDNF in renal and enteric nervous system development, significant cross-talk between GDNF and other GFR alpha coreceptors must occur in other neuronal populations [9].

Chemical compound and disease context of Rapgef5


Biological context of Rapgef5

  • From day 6 through day 14, the MAP had increased (P < 0.01) in AngII400, accompanied by a significant reduction in GFR to 1.05 +/- 0.04 ml. min(-1). g(-1) (P < 0.01) and elevation of renal vascular resistance (RVR) (day 6 versus day 14, 15.3 +/- 0.6 versus 19.2 +/- 1.2 mmHg. ml(-1). min(-1). g(-1); P < 0.05) [13].
  • Inulin and para-aminohippurate clearances were used to assess GFR and renal plasma flow (RPF) in three groups of male C57Bl/6 mice anesthetized with inactin (100 mg/kg, intraperitoneally) and ketamine (10 mg/kg) [14].
  • In other WT animals, TP-antagonist treatment for 2 h before intravenous LPS abolished the early renal vasoconstriction and alleviated the decrease in GFR [15].
  • In wild-type mice, pentoxifylline protected against the fall in glomerular filtration rate (GFR; 105.2 +/- 6.6 vs. 50.2 +/- 6.6 mul/min, P < 0.01) at 16 h of LPS administration (2.5 mg/kg ip) [11].
  • In contrast, mice treated with i.v. carboplatin or p.o. ammine/amine Pt(IV) dicarboxylates had urinary glucose, urinary protein, GFR and kidney histology within the control range [12].

Anatomical context of Rapgef5


Associations of Rapgef5 with chemical compounds

  • L-NAME reduced GFR in AT(2) -/- to 0.87 +/- 0.07 ml/min per g of kidney wt [18].
  • The fall in GFR appears to be hemodynamically mediated by thromboxane A2 [4].
  • The data indicate that nNOS in MD tonically attenuates the GFR-lowering influence of ambient luminal NaCl, which may serve to increase the fluid and electrolyte load to the distal tubule, consistent with a role of MD nNOS in tubuloglomerular feedback resetting [19].
  • Among the vasoconstrictor challenges, only NE ameliorated the decrease in GFR 14 h after LPS injection [1].
  • Even more remarkable, eNOS(-/-) C57BLKS db/db exhibited decreases in GFR to levels <50% of that in eNOS(+/+) C57BLKS db/db, as confirmed by increased serum creatinine [20].

Analytical, diagnostic and therapeutic context of Rapgef5

  • To investigate the usage of these coreceptors for GDNF signaling in vivo, gene targeting was used to produce mice lacking the GFR alpha1 coreceptor [9].
  • When studied at day 6, the MAP of AngII400 rats was not elevated (88 +/- 2 mmHg; NS versus vehicle), yet the GFR was higher (1.05 +/- 0.05 versus 1.25 +/- 0.05 ml. min(-1). g(-1); P < 0.05) accompanied by an increase in the filtration fraction (FF) (28.8 +/- 1.2 versus 37.2 +/- 0.8%; P < 0.001) [13].
  • MAP in the control group was 77 +/- 2 mmHg; volume expansion alone did not change MAP significantly (83 +/- 2 mmHg), but led to significantly greater values in both GFR and RPF (1.35 +/- 0.14 versus 1.01 +/- 0.1 ml/min x g and 11.26 +/- 1.39 versus 6.29 +/- 0.5 ml/min x g, respectively) [14].
  • Parathyroid hormone increased significantly 3 days after nephrectomy and peaked at 2 wk, despite reduction in GFR of < 50% [21].
  • Using free-flow micropuncture techniques, the proximal-distal single-nephron GFR difference was found to be augmented in aquaporin-1 and Na/H exchanger-3 knockout mice, suggesting TGF activation in these strains of mice [22].


  1. Maintenance of renal vascular reactivity contributes to acute renal failure during endotoxemic shock. Boffa, J.J., Arendshorst, W.J. J. Am. Soc. Nephrol. (2005) [Pubmed]
  2. Early dietary protein restriction slows disease progression and lengthens survival in mice with polycystic kidney disease. Tomobe, K., Philbrick, D., Aukema, H.M., Clark, W.F., Ogborn, M.R., Parbtani, A., Takahashi, H., Holub, B.J. J. Am. Soc. Nephrol. (1994) [Pubmed]
  3. Regulation of Renal Sodium Transporters during Severe Inflammation. Schmidt, C., Höcherl, K., Schweda, F., Kurtz, A., Bucher, M. J. Am. Soc. Nephrol. (2007) [Pubmed]
  4. The functional and structural changes of the glomerulus throughout the course of murine lupus nephritis. Kiberd, B.A. J. Am. Soc. Nephrol. (1992) [Pubmed]
  5. Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice. Castrop, H., Huang, Y., Hashimoto, S., Mizel, D., Hansen, P., Theilig, F., Bachmann, S., Deng, C., Briggs, J., Schnermann, J. J. Clin. Invest. (2004) [Pubmed]
  6. GFR alpha3, a component of the artemin receptor, is required for migration and survival of the superior cervical ganglion. Nishino, J., Mochida, K., Ohfuji, Y., Shimazaki, T., Meno, C., Ohishi, S., Matsuda, Y., Fujii, H., Saijoh, Y., Hamada, H. Neuron (1999) [Pubmed]
  7. Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Heuckeroth, R.O., Enomoto, H., Grider, J.R., Golden, J.P., Hanke, J.A., Jackman, A., Molliver, D.C., Bardgett, M.E., Snider, W.D., Johnson, E.M., Milbrandt, J. Neuron (1999) [Pubmed]
  8. Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor. Rossi, J., Luukko, K., Poteryaev, D., Laurikainen, A., Sun, Y.F., Laakso, T., Eerikäinen, S., Tuominen, R., Lakso, M., Rauvala, H., Arumäe, U., Pasternack, M., Saarma, M., Airaksinen, M.S. Neuron (1999) [Pubmed]
  9. GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R.O., Snider, W.D., Johnson, E.M., Milbrandt, J. Neuron (1998) [Pubmed]
  10. Nephron function in transgenic mice with selective vascular or tubular expression of Angiotensin-converting enzyme. Kessler, S.P., Hashimoto, S., Senanayake, P.S., Gaughan, C., Sen, G.C., Schnermann, J. J. Am. Soc. Nephrol. (2005) [Pubmed]
  11. Pentoxifylline protects against endotoxin-induced acute renal failure in mice. Wang, W., Zolty, E., Falk, S., Basava, V., Reznikov, L., Schrier, R. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  12. Lack of nephrotoxicity of oral ammine/amine platinum (IV) dicarboxylate complexes in rodents. McKeage, M.J., Morgan, S.E., Boxall, F.E., Murrer, B.A., Hard, G.C., Harrap, K.R. Br. J. Cancer (1993) [Pubmed]
  13. A mouse model of angiotensin II slow pressor response: role of oxidative stress. Kawada, N., Imai, E., Karber, A., Welch, W.J., Wilcox, C.S. J. Am. Soc. Nephrol. (2002) [Pubmed]
  14. Renal function in mice: effects of volume expansion and angiotensin II. Cervenka, L., Mitchell, K.D., Navar, L.G. J. Am. Soc. Nephrol. (1999) [Pubmed]
  15. Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice. Boffa, J.J., Just, A., Coffman, T.M., Arendshorst, W.J. J. Am. Soc. Nephrol. (2004) [Pubmed]
  16. GFR alpha2/neurturin signalling regulates noxious heat transduction in isolectin B4-binding mouse sensory neurons. Stucky, C.L., Rossi, J., Airaksinen, M.S., Lewin, G.R. J. Physiol. (Lond.) (2002) [Pubmed]
  17. Real-time measurement of kidney tubule fluid nitric oxide concentrations in early diabetes: disparate changes in different rodent models. Levine, D.Z., Iacovitti, M. Nitric Oxide (2006) [Pubmed]
  18. Pressure natriuresis in AT(2) receptor-deficient mice with L-NAME hypertension. Obst, M., Gross, V., Janke, J., Wellner, M., Schneider, W., Luft, F.C. J. Am. Soc. Nephrol. (2003) [Pubmed]
  19. Feedback control of glomerular vascular tone in neuronal nitric oxide synthase knockout mice. Vallon, V., Traynor, T., Barajas, L., Huang, Y.G., Briggs, J.P., Schnermann, J. J. Am. Soc. Nephrol. (2001) [Pubmed]
  20. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. Zhao, H.J., Wang, S., Cheng, H., Zhang, M.Z., Takahashi, T., Fogo, A.B., Breyer, M.D., Harris, R.C. J. Am. Soc. Nephrol. (2006) [Pubmed]
  21. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. Sawaya, B.P., Koszewski, N.J., Qi, Q., Langub, M.C., Monier-Faugere, M.C., Malluche, H.H. J. Am. Soc. Nephrol. (1997) [Pubmed]
  22. Micropuncture analysis of tubuloglomerular feedback regulation in transgenic mice. Schnermann, J. J. Am. Soc. Nephrol. (1999) [Pubmed]
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