Name: a murine model of irreversible and reversible unilateral ureteric obstruction
Uploaded: 2014-12-20T15:00:00
Description: Watch this Scientific Journal Video about A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction at JoVE.com

The present study was supported by grants from Kidney Research UK (ST4/2011), the Cunningham Trust (CT11/14), the Mrs AE Hogg Charitable Trust for Kidney Research and the Renal Endowment Fund of the Royal Infirmary of Edinburgh.

Diretrizes gerais: Experimentos em animais foram realizados de acordo com as diretrizes e normas impostas pelos Animais (Scientific Procedures) Act de 1986. Este protocolo eo protocolo de vídeo que acompanha são tanto para a UUO padrão e um R-UUO, que pode ser realizada em muitos linhagens de camundongos. No vídeo acompanhante, ambos os processos são realizados em ratos machos C57BL / 6 machos com idade de 8 semanas. Os dados apresentados na seção de resultados representativos foram obtidos a partir do sexo mascu...

<ol>
	<li>Chevalier, R. L., Forbes, M. S., Thornhill, B. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ureteral+obstruction+as+a+model+of+renal+interstitial+fibrosis+and+obstructive+nephropathy.">Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy.</a> Kidney Int. 75, 1145-1152 (2009).</li><li>Kipari, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nitric+oxide+is+an+important+mediator+of+renal+tubular+epithelial+cell+death+in+vitro+and+in+murine+experimental+hydronephrosis.">Nitric oxide is an important mediator of renal tubular epithelial cell death in vitro and in murine experimental hydronephrosis.</a> Am J Pathol. 169, 388-399 (2006).</li><li>Henderson, N. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Galectin-3+expression+and+secretion+links+macrophages+to+the+promotion+of+renal+fibrosis.">Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis.</a> Am J Pathol. 172, 288-298 (2008).</li><li>Kitamoto, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+liposome+clodronate+on+renal+leukocyte+populations+and+renal+fibrosis+in+murine+obstructive+nephropathy.">Effects of liposome clodronate on renal leukocyte populations and renal fibrosis in murine obstructive nephropathy.</a> J Pharmacol Sci. 111, 285-292 (2009).</li><li>Tapmeier, T. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reimplantation+of+the+ureter+after+unilateral+ureteral+obstruction+provides+a+model+that+allows+functional+evaluation.">Reimplantation of the ureter after unilateral ureteral obstruction provides a model that allows functional evaluation.</a> Kidney Int. 73, 885-889 (2008).</li><li>Cochrane, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Renal+structural+and+functional+repair+in+a+mouse+model+of+reversal+of+ureteral+obstruction.">Renal structural and functional repair in a mouse model of reversal of ureteral obstruction.</a> J Am Soc Nephrol. 16, 3623-3630 (2005).</li><li>Puri, T. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+kidney+disease+induced+in+mice+by+reversible+unilateral+ureteral+obstruction+is+dependent+on+genetic+background.">Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background.</a> Am J Physiol Renal Physiol. 298, F1024-F1032 (2010).</li><li>Heikkila, J., Holmberg, C., Kyllonen, L., Rintala, R., Taskinen, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+risk+of+end+stage+renal+disease+in+patients+with+posterior+urethral+valves.">Long-term risk of end stage renal disease in patients with posterior urethral valves.</a> J Urol. 186, 2392-2396 (2011).</li><li>Ravanan, R., Tomson, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Natural+history+of+postobstructive+nephropathy:+a+single-center+retrospective+study.">Natural history of postobstructive nephropathy: a single-center retrospective study.</a> Nephron Clin Pract. 105, c165-c170 (2007).</li><li>Bascands, J. L., Schanstra, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Obstructive+nephropathy:+insights+from+genetically+engineered+animals.">Obstructive nephropathy: insights from genetically engineered animals.</a> Kidney Int. 68, 925-937 (2005).</li><li>Park, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Postobstructive+regeneration+of+kidney+is+derailed+when+surge+in+renal+stem+cells+during+course+of+unilateral+ureteral+obstruction+is+halted.">Postobstructive regeneration of kidney is derailed when surge in renal stem cells during course of unilateral ureteral obstruction is halted.</a> Am J Physiol Renal Physiol. 298, F357-F364 (2010).</li><li>Manson, S. R., Niederhoff, R. A., Hruska, K. A., Austin, P. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endogenous+BMP-7+is+a+critical+molecular+determinant+of+the+reversibility+of+obstruction-induced+renal+injuries.">Endogenous BMP-7 is a critical molecular determinant of the reversibility of obstruction-induced renal injuries.</a> Am J Physiol Renal Physiol. 301, F1293-F1302 (2011).</li><li>Manson, S. R., Niederhoff, R. A., Hruska, K. A., Austin, P. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+BMP-7-Smad1/5/8+pathway+promotes+kidney+repair+after+obstruction+induced+renal+injury.">The BMP-7-Smad1/5/8 pathway promotes kidney repair after obstruction induced renal injury.</a> J Urol. 185, 2523-2530 (2011).</li><li>Chaves, L. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contrasting+effects+of+systemic+monocyte/macrophage+and+CD4++T+cell+depletion+in+a+reversible+ureteral+obstruction+mouse+model+of+chronic+kidney+disease.">Contrasting effects of systemic monocyte/macrophage and CD4+ T cell depletion in a reversible ureteral obstruction mouse model of chronic kidney disease.</a> Clin Dev Immunol. 2013, 836-989 (2013).</li><li>Haque, M. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+changes+in+MRI+markers+in+a+reversible+unilateral+ureteral+obstruction+mouse+model:+preliminary+experience.">Longitudinal changes in MRI markers in a reversible unilateral ureteral obstruction mouse model: preliminary experience.</a> J Magn Reson Imaging. 39, 835-841 (2014).</li><li>Bai, Z. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterially+transplanted+mesenchymal+stem+cells+in+a+mouse+reversible+unilateral+ureteral+obstruction+model:+in+vivo+bioluminescence+imaging+and+effects+on+renal+fibrosis.">Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis.</a> Chinese Med J. 126, 1890-1894 (2013).</li><li>Chaabane, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Renal+functional+decline+and+glomerulotubular+injury+are+arrested+but+not+restored+by+release+of+unilateral+ureteral+obstruction+(UUO).">Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO).</a> Am J Physiol Renal Physiol. 304, F432-F439 (2013).</li><li>Thornhill, B. A., Burt, L. E., Chen, C., Forbes, M. S., Chevalier, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variable+chronic+partial+ureteral+obstruction+in+the+neonatal+rat:+a+new+model+of+ureteropelvic+junction+obstruction.">Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction.</a> Kidney Int. 67, 42-52 (2005).</li><li>Thornhill, B. A., Chevalier, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variable+partial+unilateral+ureteral+obstruction+and+its+release+in+the+neonatal+and+adult+mouse.">Variable partial unilateral ureteral obstruction and its release in the neonatal and adult mouse.</a> Methods Mol Biol. 886, 381-392 (2012).</li></ol>

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. The R-UUO model is of relevance to human disease as patients often present with obstruction of the renal tract secondary to prostatic hypertrophy, posterior urethral valves etc. that requires decompression with patients commonly left with significant residual kidney impairment that has no current treatment options and may eventually lead to end stage kidney disease.8,9 The models detailed here enable ...

The overall aim of the experimental model described here is to induce obstructive nephropathy by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). A simple irreversible model of UUO is presented in which the left ureter is permanently obstructed by ligation with a suture or by the application of a ligating clip. This results in marked dilatation of the ureter together with reduced renal blood flow and glomerular filtration. Renal histology demonstrates tubular dilatation and increasingly severe interstitial renal inflammation and fibrosis. Irreversible UUO is a useful model and has been adopted by many researchers in the study of both renal inflammation and fibrosis.1-4 Although the irreversible model of UUO requires some surgical expertise it is relatively straightforward and is often used to seek insights into the pathogenesis of interstitial renal injury and the ensuing fibrosis. Also presented is a less frequently used R-UUO model using a modification of the method originally described by Tapmeier et al.5 The R-UUO model has much future potential for the study of inflammatory and immune processes, cellular and tissue regeneration as well as the subsequent tissue remodeling following the removal of an injurious stimulus. 
The more challenging R-UUO model has been used by a limited number of investigators with some groups employing a significantly different surgical technique to that described here6,7 though with interesting results. In the R-UUO model presented, the ureter is ligated to induce complete ureteric obstruction for a period of time sufficient to induce the level of injury and fibrosis desired: 7 days of UUO was chosen in the method described here. The ureteric obstruction is reversed and the kidney is allowed to decompress for a period of time determined by the investigator before the mice are culled and the kidney removed for analysis: 7 days of decompression was chosen in the method described here though a longer period would be chosen if the resolution of inflammation and fibrosis was being studied. Although the method described here requires significant surgical expertise, it offers several advantages over other R-UUO models. The application of soft walled plastic tubing to the obstructed ureter prevents excessive ureteric dilation and this facilitates the subsequent manipulation and anastomosis of the ureter. Furthermore, in the described R-UUO model the ureter is divided thereby allowing the removal of any residual urinary sediment and debris. This confirms that the remaining ureter lumen is de-obstructed and patent prior to anastomosis to the bladder. 
Experiments incorporating both the irreversible and reversible UUO models can provide researchers with a powerful insight into the molecular and cellular mechanisms of both injury and subsequent resolution and regeneration. Thus, the model of R-UUO described here would be highly relevant to researchers interested in post-inflammatory tissue remodeling and how this can be modulated.

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			<td>Blunt Dissecting Scissors</td>
			<td>Fine Science Tools</td>
			<td>14072-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Spring Scissors &#8211; straight</td>
			<td>Fine Science Tools</td>
			<td>15000-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Toothed forceps</td>
			<td>Fine Science Tools</td>
			<td>11021-12</td>
			<td></td>
		</tr>
		<tr>
			<td>Angled forceps x 2</td>
			<td>Fine Science Tools</td>
			<td>00649-11</td>
			<td></td>
		</tr>
		<tr>
			<td>Straight forceps</td>
			<td>Fine Science Tools</td>
			<td>00632-11</td>
			<td></td>
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		<tr>
			<td>Colibri 3cm wire retractor</td>
			<td>Fine Science Tools</td>
			<td>17000-03</td>
			<td></td>
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			<td>Castroviejo needle holder with lock</td>
			<td>Fine Science Tools</td>
			<td>12565-14</td>
			<td></td>
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		<tr>
			<td>Wound clip applicator</td>
			<td>Fine Science Tools</td>
			<td>12031-07</td>
			<td></td>
		</tr>
		<tr>
			<td>7mm wound clips</td>
			<td>Fine Science Tools</td>
			<td>12032-07</td>
			<td></td>
		</tr>
		<tr>
			<td>Castroviejo micro needle holder with lock</td>
			<td>Fine Science Tools</td>
			<td>12060-01</td>
			<td></td>
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			<td>OPMI pico microscope</td>
			<td>Carl Zeiss</td>
			<td>S100</td>
			<td></td>
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			<td>Heat electronic pad</td>
			<td>Cozee Comfort</td>
			<td>n/a</td>
			<td></td>
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		<tr>
			<td>6/O silk braided suture</td>
			<td>Harvard Apparatus</td>
			<td>72-3287</td>
			<td></td>
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		<tr>
			<td>9/O Dafilon (polyamide) suture</td>
			<td>B-Braun</td>
			<td>G1111434</td>
			<td></td>
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		<tr>
			<td>5/O braided silk suture</td>
			<td>Harvard Apparatus</td>
			<td>51-7680</td>
			<td></td>
		</tr>
		<tr>
			<td>Regular bevel needle, 1 inch, 21G</td>
			<td>Becton, Dickinson and Company</td>
			<td>305175</td>
			<td></td>
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		<tr>
			<td>1 ml syringe slip tip</td>
			<td>Becton, Dickinson and Company</td>
			<td>300184</td>
			<td></td>
		</tr>
		<tr>
			<td>Wypall paper swabs</td>
			<td>Kimberley-Clark</td>
			<td>L40</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Cotton wool buds</td>
			<td>Johnson and Johnson</td>
			<td>n/a</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Plain drapes</td>
			<td>Guardian</td>
			<td>CB03</td>
			<td>Sterilised (Autoclave)</td>
		</tr>
		<tr>
			<td>Soft wall silicone rubber tubing</td>
			<td></td>
			<td></td>
			<td>Silicone tubing - internal diameter 1.0 mm; external diameter 2.0 mm; wall thickness 0.6 mm</td>
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			<td>(Lacri-Lube) White soft paraffin 57.3%, mineral oil 42.5% and lanolin alcohols 0.2%</td>
			<td>Allergan Ltd</td>
			<td>21956GB10X</td>
			<td></td>
		</tr>
		<tr>
			<td>(Videne) Povidone-iodine 10%</td>
			<td>Ecolab Ltd</td>
			<td>PL 04509/0041</td>
			<td></td>
		</tr>
		<tr>
			<td>(Vetalar V) Ketamine hydrochloride</td>
			<td>Pfizer Animal Health</td>
			<td>Vm 42058/4165</td>
			<td>100mg/ml solution</td>
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			<td>(Domitor) Medetomidine hydrochloride</td>
			<td>Orion Pharma</td>
			<td>Vm 06043/4003</td>
			<td>1mg/ml</td>
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			<td>(Vetergesic) Bupernorphine hydrochloride</td>
			<td>Alsto Animal Health</td>
			<td>Vm 00063/4002</td>
			<td>0.3mg/ml</td>
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			<td>(Antisedan) Atipamezole hydrochoride</td>
			<td>Orion Pharma</td>
			<td>Vm 06043/4004</td>
			<td>5mg/ml</td>
		</tr>
		<tr>
			<td>(Adept) 4% Icodextrin</td>
			<td>Baxter</td>
			<td></td>
			<td>Adhesion reduction solution</td>
		</tr>
		<tr>
			<td>NaCl 0.9%</td>
			<td>Baxter</td>
			<td>FKE1323</td>
			<td></td>
		</tr>
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a murine model of irreversible and reversible unilateral ureteric obstruction

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure.

A aparência das alterações renais marcadamente após obstrução ureteral e torna-se mais pálida e tenso para a palpação com o tempo (Figura 1). Há cada vez mais a dilatação do ureter proximal à obstrução e da pelve renal. O rim torna-se cada vez mais atrófica como a duração da nefropatia obstrutiva aumenta com a obstrução prolongada resultando em um desbaste significativo do córtex e na medula renal. Após a reversão da obstrução ureteral, a cor do rim torna-se mais escura que aume...

Watch this Scientific Journal Video about A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction at JoVE.com

A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

The murine model of irreversible unilateral ureteric obstruction (UUO) is presented together with the model of reversible UUO in which the ureteric obstruction is relieved by anastomosis of the severed ureter into the bladder. These models enable the study of renal inflammation and scarring as well as tissue remodeling.

Um modelo murino de irreversível e reversível obstrução ureteral unilateral

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive ...

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