Knockout mice help find gene for bad breath
An international team of researchers has identified a cause for chronic bad breath (halitosis), with the help of gene knockout mice from the UC Davis Mouse Biology Program. The results are published Dec. 18 in the journal Nature Genetics.
While most cases of bad breath are linked bacteria growing in the mouth, up to 3 percent of the population have chronic halitosis of no obvious cause.
"It's important to identify the cause of persistent halitosis, and differentiate that cause from relatively benign causes (e.g., gum disease) and the more morbid causes such as liver cirrhosis," said Professor Kent Lloyd, director of the Mouse Biology Program at UC Davis.
Researchers at Radboud University in The Netherlands have been studying families with chronic bad breath for several years. They found that these people produced a lot of sulfur-based compounds in their breath, especially methanethiol which has an unpleasant boiled-cabbage smell. Methanethiol is normally produced during digestion but broken down in the body.
Some bacteria can break down sulfur compounds. Based on bacterial genes, the team identified a human protein, selenium binding protein 1, which can convert methanethiol into other and compounds.
Sulfur compounds in blood
When they looked at their human patients, they found that all had mutations in the SELENBP1 gene that produces this protein and they all had high levels of methanethiol and dimethyl sulfide in their blood. When blood reaches the lungs, these smelly sulfur compounds leave the blood and are exhaled in breath.
Similarly, mice with a genetic knockout of the mouse equivalent of SELENBP1 had low levels of the protein and high levels of methanethiol and other volatile sulfur compounds in their blood.
"While we didn't put our noses up to the mice's mouths, we did measure high amounts of some of these odor-forming chemicals in their blood, matching precisely what was found in the patients," Lloyd said.
SELENBP1 has also been associated with some cancers in human, although it is not clear how this works. Currently there is no treatment for this form of halitosis, but the genetic studies and a better understanding of sulfur metabolism might lead to treatments in the future.
Authors on the study in addition to Lloyd and Renee S. Araiza at the UC Davis Mouse Biology Program were: at Radboud University, Ron A. Wevers, Huub J. M. Op den Camp, Arjan Pol, G. Herma Renkema, Albert Tangerman, Udo F. Engelke, Lambert van den Heuvel, Marijn Oude Elberink, Christian Gilissen, Richard J. Rodenburg, Arjan P. M. de Brouwer and Hanka Venselaar; Edwin G. Winkel, University of Groeningen; Heymut Omran and Heike Olbrich, Universitätsklinikum Münster, Germany; Jörn Oliver Sass, Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany; K. Otfried Schwab, University Hospital Freiburg, Germany; Hendrik Schäfer, University of Warwick, U.K.; and J. Silvia Sequeira, Hospital de Dona Estefânia, Lisbon, Portugal.
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