title: Short-lived mammals (shrew, mouse) have a less robust metal-responsive transcription factor than humans and bats.
abstract: Non-essential "heavy" metals such as cadmium tend to accumulate in an organism and thus are a particular threat for long-lived animals. Here we show that two unrelated, short-lived groups of mammals (rodents and shrews, separated by 100 Mio years of evolution) each have independently acquired mutations in their metal-responsive transcription factor (MTF-1) in a domain relevant for robust transcriptional induction by zinc and cadmium. While key amino acids are mutated in rodents, in shrews an entire exon is skipped. Rodents and especially shrews are unique regarding the alterations of this region. To investigate the biological relevance of these alterations, MTF-1s from the common shrew (Sorex araneus), the mouse, humans and a bat (Myotis blythii), were tested by cotransfection with a reporter gene into cells lacking MTF-1. Whereas shrews only live for 1.5-2.5 years, bats, although living on a very similar insect diet, have a lifespan of several decades. We find that bat MTF-1 is similarly metal-responsive as its human counterpart, while shrew MTF-1 is less responsive, similar to mouse MTF-1. We propose that in comparison to most other mammals, the short-lived shrews and rodents can afford a "lower-quality" system for heavy metal homeostasis and detoxification.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057, Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057, Zurich, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Steiner
authors.affiliation: National Museum of Natural History, 1000, Sofia, Bulgaria.
authors.forename: Boyan
authors.initials: B
authors.lastname: Petrov
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057, Zurich, Switzerland. oleg.georgiev@imls.uzh.ch.
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057, Zurich, Switzerland. walter.schaffner@imls.uzh.ch.
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002685:Chiroptera / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008017:Life Expectancy; D051379:Mice; D012788:Shrews / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D015533:Transcriptional Activation; D015032:Zinc / Q000378:metabolism*; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1
keywords: Cadmium toxicity; Longevity; Metal homeostasis; Metal regulatory transcription factor; Zinc-induced transcription