Disease relevance of Cys1

• Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice [1].
• Development of autosomal recessive polycystic kidney disease in BALB/c-cpk/cpk mice [2].
• EGF treatment did not prevent renal failure but ameliorated pathologic changes in the kidney and the biliary ducts of the BALB/c-cpk/cpk mouse [2].
• To examine this activity, we cultured cystic kidney tubules derived from the C57BL/6J cpk/cpk mouse, a hereditary model of polycystic kidney disease, and assayed conditioned medium for the presence of MMPs and tissue inhibitors of metalloproteinases (TIMPs) [3].
• Modification of the alpha-amino group of Cys1 and of the epsilon-amino group of Lys4 by acetic anhydride or fluorescamine decreased toxicity only by a factor of 2.5-2 [4].

Psychiatry related information on Cys1

• To determine if the lack of EGF may be a decisive factor in the initiation and/or growth of collecting duct cysts, we administered exogenous EGF (1 microgram/g body wt subcutaneously) daily for Postnatal Days 3-9 (a critical period for collecting duct maturation) to C57BL/6J-cpk mice [5].

High impact information on Cys1

• Our results indicate that the microtubule cytoskeleton has a central role in the pathogenesis of PKD in cpk mice and that taxol may also be useful in treating human PKD [6].
• This is associated with abnormal development of primary cilia at the apical pole of the duct cells and with reduced expression of a set of genes involved in polycystic diseases, namely those coding for HNF-1beta and for the cilium-associated proteins polyductin/fibrocystin and cystin [7].
• Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age [8].
• The current study was designed: (i) to characterize the cpk-associated biliary disease in affected F(2) homozygotes from intercrosses with either CAST or D2; and (ii) to evaluate focal biliary cysts identified in heterozygotes from a D2-cpk congenic strain [9].
• Genetic analysis demonstrated loss of heterozygosity at the cpk interval and supports a loss-of-function model for biliary cysts [9].

Chemical compound and disease context of Cys1

• Mice homozygous for the mutation cpk develop a lethal infantile polycystic kidney disease (PKD) and have abnormal elevations of corticosterone in the postnatal period [10].

Biological context of Cys1

• The present study examined the ontogeny of renal and submandibular gland prepro-epidermal growth factor (preproEGF) gene expression in the cpk mouse using Northern blot hybridization and immunohistochemistry [11].
• To investigate whether antiapoptotic action of TIMP-1 was mediated through its inhibition on MMP activities, we constructed mutant TIMP-1 by side-directed mutagenesis, which abolished the inhibitory activity of MMPs by deletion of Cys1 to Ala4 [12].
• Expression of the biliary lesion is modulated by genetic background, and the specific biliary phenotype is determined by whether loss of function of the cpk gene occurs as a germline or a somatic event [9].
• Elevated proto-oncogene expression in polycystic kidneys of the C57BL/6J (cpk) mouse [13].
• In contrast, in cpk mice, ectopic expression of Cux-1 is associated with apoptosis [14].

Anatomical context of Cys1

• Matrix metalloproteinases and TIMPS in cultured C57BL/6J-cpk kidney tubules [3].
• Between approximately 1 and 3 weeks of age, affected cpk mice develop numerous large cysts in the collecting tubule segment of kidney nephrons [11].
• We determined in the cpk mouse that the testes similar to the immature ovaries, is also under-developed and arrested at an early developmental stage [15].
• We conclude that Cys1 and Cys3 are not absolutely necessary for membrane binding or plasma membrane localization [16].
• Syndet C1S/C3S, with substitutions at the pair Cys1 and Cys3, distributes to the plasma membrane, a Golgi-like compartment, and the cytosol [16].

Associations of Cys1 with chemical compounds

• This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse [17].
• Arrested testis development in the cpk mouse may be the result of abnormal steroid metabolism [15].
• Among the cysteine replacement analogs, the double mutation of Cys1 and 15 to Ser resulted in significantly increased stability without compromising the mitogenic activity, while Cys to Ser mutations at other positions were either destabilizing or had no effect [18].
• In addition, the plasma corticosterone levels are higher in a heritable murine model of polycystic kidney disease, cpk mice, in the first postnatal week [19].
• Aberrant 11beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: implications for regulation by the Ke 6 gene [19].

Regulatory relationships of Cys1

• The overexpression and/or overactivity of the AVP-V2R appears to contribute to the progression of PKD since an AVP-V2R antagonist inhibits cystic renal enlargement in the cpk mouse [20].
• We report here that the Ke 6 gene and the 11 beta-HSD gene are regulated in the same aberrant pattern in the cpk mouse [21].

Other interactions of Cys1

• METHODS: RNA was isolated from kidney, liver and pancreas of cystic and normal BALB/c-cpk mice [22].
• We have also examined the expression of the SGP-2 gene in polycystic kidneys of the C57BL/6J-cpk mouse, a model of autosomal recessive polycystic kidney disease in which there is development of epithelial-lined cysts arising primarily from the collecting duct system [23].
• In this report, Pax2 expression is demonstrated in the cystic epithelium of the mouse cpk kidneys [24].
• CONCLUSION: These results suggest that cyst development in Pkd1 null mice and cpk mice proceeds through different mechanisms [14].
• Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse [25].

Analytical, diagnostic and therapeutic context of Cys1

• Therefore, renal expression of EGF receptor (EGFR) protein and mRNA was examined in an animal model for ARPKD, the C57BL/6Jcpk/cpk (CPK) mouse [26].
• In this study, tenascin expression was studied by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice [27].
• We have isolated Drosophila and murine genes (termed cpk and cpk-m respectively) by polymerase chain reaction amplification of cDNA libraries with degenerate primers corresponding to conserved regions of PtdIns kinases [28].

References