Genetic regulation of slowly progressing mild muscle atrophy in fast-twitch muscles of BUF/Mna rats

Amo, Hiroyuki; Saito, Mitsuhiro; Nagao, Shizuko; Yagiu, Shigeru; Takahashi, Hisahide; Morita, Hiroyuki; Morita, Takako; Matsuyama, Mutsushi

doi:10.1002/(sici)1097-4598(199710)20:10<1258::aid-mus8>3.0.co;2-b

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…32,33 Furthermore, BUF rats show muscle atrophy, fatigability and weakness. 34,35 Cosegregation and linkage analyses Linkage analysis in a male (BUF Â Wistar Kyoto (WKY)/NCrj) F1 Â BUF backcross population revealed significant linkage only to one locus, that is, the QTL Pur1 (Proteinuria QTL 1) on rat chromosome (RNO)13 linked to the development of proteinuria (Tables 1 and 5). 24 Interestingly, this QTL explained about 39% of the total variance of proteinuria in the backcross population.…”

Section: Buffalo 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: Buffalo Rat Strain Breedingmentioning

confidence: 99%

Mapping genetic determinants of kidney damage in rat models

Schulz

Kreutz

2012

Hypertens Res

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“…Thus, we would suggest that both the slowly progressing muscle atrophy [1] and age-dependent turnover of muscle fibers [11,30] coexist in the aged thymoma rats. The mechanism of how the remodeling of NMJs seen in BUF/Mna rats is induced, however, still remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the occurrence of the autoantibodies does not appear to correlate directly with the thymoma development, since thymomas in male BUF/Mna rats start to develop at about 9 months of age [10]. Since the muscle atrophy develops slowly [1], it may take such a long period until the fine structural changes of SNAs become evident. Alternatively, it has been known that this strain of rats complicates abnormal lipid metabolism and hypoproteinemia with creatinuria, which could be a possible cause of muscle weakness and fatigability and variable changes in muscle fibers [18].…”

Section: Discussionmentioning

confidence: 99%

Age changes of neuromuscular junctions in the extensor digitorum longus muscle of spontaneous thymoma BUF/Mna rats

et al. 2000

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BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.

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“…Rats of the BUF/Mna (BUF) strain develop thymus hyperplasia, thymoma, muscle atrophy, and proteinuria in almost 100% [1][2][3][4][5][6][7][8][9][10]. During the course of the experiment on proteinuria, we incidentally found that some of old male rats of this strain refused to take food in isolated metabolic cages.…”

Section: Introductionmentioning

confidence: 92%