Strain-dependent differences in electrogenic secretion of electrolytes across mouse colon epithelium.
Mice have proven to be powerful models for the study of human physiology and pathophysiology. With the advent of techniques for genomic manipulation, the possibilities for studying inherited diseases in this convenient laboratory mammal are increasing by the day. It has been reported that when knocking out or otherwise modifying genes of interest in mice, the phenotype obtained can vary markedly depending on the genetic background of the animals used in the study. The aim of this work was to study whether the genetic background can influence the characteristics of fluid and electrolyte transepithelial transport in the distal colon of three mouse strains most in use in our and other laboratories. Ussing chamber recordings revealed that the colons of C57Bl/6J, Sv 129 and Black Swiss animals have distinctive responses to the calcium agonists carbachol and histamine that are not explained by the presence of different types of muscarinic and histaminergic receptors in these tissues. We have also found differences in the cAMP-activated, KCNMA1-channel-dependent potassium secretion between the strains. We interpret this to indicate a unique distribution of KCNMA1 channels in lower parts of the crypt of Sv 129 colonic epithelium compared with that of C57Bl/6J and Black Swiss animals. The reported differences should be taken into account when choosing the genetic background of animals to be used for genetic modification.
Flores
Carlos A
CA
Centro de Estudios Científicos (CECS), Avenida Arturo Prat 514, Valdivia 5110466, Chile.
Cid
L Pablo
LP
Sepúlveda
Francisco V
FV
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D004573:Electrolytes / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000235:genetics / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects; D064506:Solute Carrier Family 12, Member 2; D014867:Water / Q000032:analysis
D004573:Electrolytes; D006633:Histamine Antagonists; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018727:Muscarinic Antagonists; D011969:Receptors, Histamine H1; D011976:Receptors, Muscarinic; C578877:SLC12A2 protein, human; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D014867:Water; D002034:Bumetanide; D005576:Colforsin; D001464:Barium; D006632:Histamine; D002217:Carbachol; D000242:Cyclic AMP; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine