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Generation of mice with targeted disruption of the A1 adenosine receptor gene and their use in studies of renal function.

dc.contributor.authorSun, Daqing
dc.contributor.advisorBriggs, Josephine
dc.contributor.advisorSchnermann, Jurgen
dc.date.accessioned2016-08-30T16:55:16Z
dc.date.available2016-08-30T16:55:16Z
dc.date.issued2001
dc.identifier.urihttp://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3029443
dc.identifier.urihttps://hdl.handle.net/2027.42/128767
dc.description.abstractAdenosine exerts a wide range of effects throughout the body, and these actions are mediated by four subtypes of adenosine receptors (A1, A2a, A2b and A3). Adenosine has been implicated to be a determinant of metabolic control of organ function. In the kidney, activation of A1 adenosine receptor (AJAR) in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of AJAR in TGF and in other aspects of renal function, we have generated and studied mice in which the entire AJAR coding sequence was deleted by homologous recombination. We found there are no apparent gross anatomical abnormalities in A1AR-/- mice. Plasma and urinary electrolytes, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR+/+, A1AR+/-, and A1AR-/- mice. However, TGF responses were completely abolished in A1AR-/- mice. Absence of TGF responses in A1AR deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues.
dc.format.extent82 p.
dc.languageEnglish
dc.language.isoEN
dc.subjectA1 Adenosine Receptor
dc.subjectAdenosine A1 Receptor
dc.subjectCardiac Cells
dc.subjectFunction
dc.subjectGene
dc.subjectGeneration
dc.subjectMice
dc.subjectRenal
dc.subjectStudies
dc.subjectTargeted Disruption
dc.subjectUse
dc.titleGeneration of mice with targeted disruption of the A1 adenosine receptor gene and their use in studies of renal function.
dc.typeThesis
dc.description.thesisdegreenamePhDen_US
dc.description.thesisdegreedisciplineAnimal Physiology
dc.description.thesisdegreedisciplineBiological Sciences
dc.description.thesisdegreedisciplineDevelopmental biology
dc.description.thesisdegreedisciplineHealth and Environmental Sciences
dc.description.thesisdegreedisciplineMolecular biology
dc.description.thesisdegreegrantorUniversity of Michigan, Horace H. Rackham School of Graduate Studies
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/128767/2/3029443.pdf
dc.owningcollnameDissertations and Theses (Ph.D. and Master's)


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