Distribution of Glomeruli in the Renal Cortex of Munich Wistar Frömter (MWF) Rats

Hackbarth, Hansjoachim; Büttner, D.; Jarck, D.; Pothmann, M.; Messow, C; Gärtner, Klaus

doi:10.1159/000172882

Cited by 21 publications

(23 citation statements)

References 7 publications

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“…128,129 The colony MWF/ FUB renamed as MWF/ Rkb and more recently to MWF/FubRkb was established in 1996 by further inbreeding of rats from the original colony at the Charité -Universitätsmedizin Berlin, Germany. 130 Strain characteristics MWF rats develop mild SS spontaneous hypertension, spontaneous albuminuria of early onset, structural renal abnormalities such as an inherited nephron reduction of 30-50%, glomerulosclerosis, reduced podocyte number, renal interstitial fibrosis and endothelial dysfunction.…”

Section: Munich Wistar Frö Mter Rat Strain Breedingmentioning

confidence: 99%

Mapping genetic determinants of kidney damage in rat models

Schulz

Kreutz

2012

Hypertens Res

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During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD. INTRODUCTIONCommon forms of chronic kidney diseases (CKD) represent complex disease phenotypes that are influenced by both environmental and genetic factors. [1][2][3][4][5] Both arterial hypertension and type-2 diabetes mellitus are major contributors to complex CKD, which has a high prevalence in the general human population worldwide affecting B11-15% of individuals in Europe and United States. 6-9 CKD represents as expected a major risk factor for the progression to end-stage renal disease but associates also with an increased risk of cardiovascular morbidity and mortality. 10,11 In addition to the assessment of impaired renal function or glomerular filtration rate, urinary albumin excretion rate (albuminuria) represents another important clinical marker for the evaluation of CKD and cardiovascular risk of patients. [10][11][12][13][14][15] These renal disease phenotypes are also inherited in several inbred rat strains many of which are hypertensive. 16 During the last decades, genetic mapping studies by genome-wide linkage analysis followed by fine mapping of selected quantitative trait loci (QTL) for renal disease phenotypes were reported. Subsequently, studies in consomic and congenic rats were performed to further unravel the genetics of kidney injury in inbred rat strains. For QTL confirmation, consomic strains were generated by transfer of an entire chromosome carrying a QTL from a donor strain into the disease backgro...

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Section: Munich Wistar Frö Mter Rat Strain Breedingmentioning

confidence: 99%

Mapping genetic determinants of kidney damage in rat models

Schulz

Kreutz

2012

Hypertens Res

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“…The glomerulosclerosis index (GSI) was assessed using a semiquantitative scoring system as previously reported, analyzing both superficial and juxtamedullary glomeruli (14 15). Two phenotypes for the presence of superficial glomeruli were determined: first, the number of surface glomeruli per section with direct contact to the surface was counted; second, all superficial glomeruli present in the renal cortex corticis zone but without direct surface contact were counted in three mid-coronal sections for each animal, respectively (16). The mean values were calculated and taken for linkage analysis.…”

Section: Phenotypingmentioning

confidence: 99%

Genetic Dissection of Increased Urinary Albumin Excretion in the Munich Wistar Fro[Combining Diaeresis]mter Rat

Schulz

Litfin²,

Koßmehl³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. An elevated urinary albumin excretion (UAE) is a risk factor for the development of chronic nephropathy and for cardiovascular mortality. The Munich Wistar Frömter (MWF) rat represents a genetic model that develops spontaneously mild hypertension and a 142-fold increased UAE compared with normal Lewis rats at 14 wk of age. The genetic basis of UAE in male MWF was analyzed in relation to BP by using a quantitative trait (QTL) mapping strategy. F1-hybrids generated from a cross between MWF and Lewis rats showed normal UAE rates similar to Lewis. A backcross strategy including 213 animals was therefore used. To account for age-of-onset effects, UAE was determined in young backcross animals at 8 wk and in adult animals at 14 and 24 wk of age, respectively. Total genome scan analysis identified three QTL with significant linkage to UAE and one QTL with suggestive linkage to UAE. These loci showed no linkage to BP, and BP explained only 2% of the total variance of UAE. Homozygosity for the MWF allele accounted for a similar mean increase in UAE in adult backcross animals at each UAE QTL. When single gene effects were analyzed, only one UAE QTL led to a significant increase in UAE. Early onset of albuminuria and a considerable increase of UAE in adult animals required homozygosity at three loci at least. This study demonstrates the polygenetic recessive determination of increased UAE by a set of genes that are unlinked to BP.An elevated urinary albumin excretion (UAE) is a predictor of the development of nephropathy (1), and a moderate increase of UAE in the range of microalbuminuria represents an independent risk factor for cardiovascular events in patients with hypertension, diabetes or preexisting cardiovascular disease (2,3). With regard to the latter it is important to point out that microalbuminuria represents a quantitative clinical phenotype such as hypertension, which is arbitrarily defined on the basis of a quantitative cut-off value (1,4). Animal strains that display an increased UAE as an inherited trait represent an attractive substitute for the dissection of the polygenetic basis of UAE. Fully inbred animal models expressing a genetically determined disease avoid the problem of genetic heterogeneity, which in humans reduces statistical power to a degree that may preclude detection of individual genetic factors (5). In addition, animal experimentation allows a much more precise control of environmental factors compared with clinical studies. Most importantly, the ability to produce specific intercrosses between strains with low and high UAE rates represents a powerful experimental tool for carrying out genetic linkage analyses. The Munich Wistar Frömter (MWF) rat represents such an inbred genetic animal model that spontaneously develops an increased UAE (6). MWF animals develop also moderate spontaneous hypertension and exhibit a lower number of nephrons compared with other rat strains (7). Although both male and female MWF animals demonstrate a similar reduction in nephron number when compared w...

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“…The advantage of using this strain is that most glomeruli are located under the vicinal surface of the kidney, and with this glomerular localization, the glomerular vessels and fluid from the Bowman's capsule are directly acces sible (12,13). Therefore, extensive pharmacological and physiological studies of glomerular characteristics have been carried out with this strain (30)(31)(32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, extensive pharmacological and physiological studies of glomerular characteristics have been carried out with this strain (30)(31)(32)(33)(34)(35)(36). With respect to the localization of glomeruli, Hackbarth et al (12) report ed that an average of 3-4 superficial glomeruli was ob served in each histological section in MW rats aged be tween 20 and 100 days, while in the control rat kidney, only 2 superficial glomeruli were found in all histological sections. They also reported that at ages of over 100 days, the number of superficial glomeruli diminished to about one per section.…”

Section: Discussionmentioning

confidence: 99%

“…In the Munich strain of Wistar rats (Munich-Wistar; MW), however, some glomeruli are located near the surface of the kidney (12,13). This unique characteristic of MW rat kidney has permitted the direct measurement of hydrostatic pressure in glomerular capillaries and Bowman's spaces, and the evaluation of various factors that may determine the glomerular filtra tion rate (14).…”

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Visualization of Renal Microcirculation in Isolated Munich-Wistar Rat Kidneys: Effects of Endothelin-1 on Renal Hemodynamic Activity

Saitō

Homma

Yamatsu

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-The aim of the present study was to visualize the superficial glomeruli of the Munich-Wistar (MW) rat and to characterize the responses of the renal microvasculature to endothelin-1 (ET-1). We first ex amined the distribution of superficial glomeruli of the MW rat compared to that in a control strain (Wistar rat). Secondly, we examined the effects of ET-1 on the renal microcirculation of the MW rat. The right kidney was perfused with a Krebs-Ringer solution containing fluorescein isothiocyanate dextran (FITC-dex tran) and was visualized under an epi-illuminated fluorescence microscope system. Changes in perfusion pressure and diameter of the microvessels accompanying the administration of ET-1 (10 fmole-300 pmole) were measured. The number of superficial glomeruli was greater in the MW rat than in the Wistar rat. ET-1 had long-lasting and dose-dependent pressor effects. Perfusion pressure showed a 3.5-fold increase com pared with the control, and the afferent arterioles showed greater dose-dependent vasoconstriction than the efferent arterioles. These findings suggest that the MW rat is a useful animal model for the study of renal microcirculation and that the renal microcirculation is extremely sensitive to ET-1.

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Distribution of Glomeruli in the Renal Cortex of Munich Wistar Frömter (MWF) Rats

Cited by 21 publications

References 7 publications

Mapping genetic determinants of kidney damage in rat models

Mapping genetic determinants of kidney damage in rat models

Genetic Dissection of Increased Urinary Albumin Excretion in the Munich Wistar Fro[Combining Diaeresis]mter Rat

Visualization of Renal Microcirculation in Isolated Munich-Wistar Rat Kidneys: Effects of Endothelin-1 on Renal Hemodynamic Activity

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