[International Pest Control] A Mouse Tale Like No Other

Features - Rodents & Mice

A hybrid species of globe-trotting mice has been found to have resistant characteristics to two widely used rodenticide active ingredients.

March 27, 2012
Jeff Fenner

What do you get when mice from two different countries breed? No, not a mouse that speaks two languages or can make a dinner recommendation in Barcelona or Berlin, but one that has “super mouse” characteristics and appears to be resistant to rodenticides.

These globe-trotting mice, discovered in research conducted by Dr. Stefan Endepols of Bayer CropScience and Dr. Michael Kohn of Rice University and colleagues, were found to have resistant characteristics to two widely used rodenticide active ingredients — bromadiolone and difencacoum.

The mice were first encountered by a pest management professional in Germany who serviced several large industrial bakeries. Bakeries can be prime locations for rodent infestations because of the abundance of food sources and the fact that rodents can gain access through the delivery of raw materials from outside suppliers.

The pest management professional was using bromadiolone to eliminate the rodents, but was not having much success. He contacted Endepols to see if he could help identify the level of resistance causing the control problem.

Super Mouse a Hit With the Media

The discovery of the super mouse strain garnered a lot of attention in the scientific press including articles in Discovery, Science Daily, Current Biology and Science magazine, to name a few.

The German and other international popular press also picked up on the story. After all, who wouldn’t be fascinated by the story of a mouse that has unique genes and is resistant to the product designed to cause its demise? “When the information came out, we heard from reporters from across the globe,” said Dr. Stefan Endepols of Bayer CropScience. “It was really quite interesting to have so much attention on the topic.”

No word from the mouse’s publicist, but sources close to the situation say they are working on a snap-trap-resistant strain next. Stay tuned.

Endepols, Bayer’s global senior scientist for rodents and rodenticides, brought several of the mice into his lab for further study, then contacted noted genetic biologist Kohn to see if he was interested in taking a look. After receiving several sample strains, Kohn determined that the DNA of the resistance gene did not belong to the common house mouse (Mus musculus domesticus) typically found in the region.

Upon further study, Kohn discovered a significant part of the mouse’s DNA came from the Algerian mouse (Mus spretus), a species appearing only in the Mediterranean region from Southern France into Spain, and definitely not native to where the mouse was trapped in Germany.

“From a biological point of view it is a remarkable finding,” said Endepols, a biologist with 20 years of experience working with rodents.

The Family Tree. Further genetic analysis revealed that an enzyme, which was the target of the rodenticide, had been acquired from the other Mediterranean mouse species during hybridization. Hybridization is the interbreeding or combining of two different species to create a type of hybrid. For example, a mule is a hybrid of a horse and donkey.

Kohn’s analysis pegged the hybridization between the Algerian mouse and its European soul mate to have taken place 15 to 20 years earlier.

Endepols said hybrid species are known to have a slim chance to reproduce, because genetic barriers work against them. Hybrids like the mule are typically sterile. However, due to the pressure from the widespread use of rodenticides, the door was opened for a new mouse strain to develop, one that acquired the resistance gene from the other species during mating.

Research has shown the house mouse has developed resistance from mutations that have taken place over generations, he said, adding that mouse species from arid areas, like the Mediterranean, often possess unique clotting genes.

Endepols pointed out that house mice around the world can possess different polymorphisms in the target gene of an anticoagulant rodenticide, but they share a common one by having only one amino acid exchanged in the enzyme. The “super mouse” species found in Germany had at least four amino acids exchanged in the enzyme. This change in the enzyme was too big to be simply a result of point mutation, the common process by which rodents and insects acquire resistance.

“It was obvious that the gene was quite strange in this species,” said Endepols. “We speculated this was something new, but did not expect this type of hybridization had created a new strain.”

What can pest management professionals learn from this discovery? Endepols said it is important that the industry continues to encourage the development of innovative customer-centric solutions based on cutting-edge product technology and good management practices.

“I think the pressure by the use of pesticides including rodenticides is great, and may be even greater when used with poor practice,” said Endepols. “When used on a large scale and not brought to an end, it can leave resistant survivors.”

Hybrid species have a slim chance to reproduce, because genetic barriers work against them.

He said the pest management industry must be prepared for new, resistant strains of organisms to appear, not only in rodents but in insects and fungi, which are quite resistant.

“It is a signal to our industry to put resources into the study of resistance, continue to develop new active ingredients, and employ new management practices in order to win the race,” said Endepols. “It is a new evolutionary way for resistance to evolve in a short time, and that’s important to know.”

He said the industry needs to build relationships between customers and stakeholders — including pest management professionals, efficacy-testing laboratories and genetic laboratories — when developing new products and conducting research.

“When we are able to establish that connection, it brings in new and amazing research and ideas,” said Endepols.

Bayer, while not a supplier of rodenticides to the U.S. market, has long been a leading player in the rodent market in Europe and Asia with Racumin, a broad range of products with the anticoagulant rodenticide active ingredient, coumatertrayl. “We have decades of successful research in rodent behavior and resistance issues,” Endepols said.

Rodent Resistance

For the last 15 years, pest professionals in Europe have been living under a growing threat of rodents resistant to second-generation anticoagulant rodenticides, but progress is being made thanks to advancements in science and technology. Researchers in Europe are using gene sequencing to understand the science behind rodenticide resistance and to map the spread of resistant rodents.

The identification of a hybrid mouse species (a cross between an Algerian mouse and house mouse) that is resistant to bromadiolone and difenacoum is helping researchers (see feature story). “The Algerian mouse is not the problem, but it’s got some mutations that are very interesting and relevant to understanding resistance in pest species,” said Alex Cornish, global technical manager for Syngenta’s Professional Pest Management business.

Anticoagulant rodenticides work by blocking the enzyme that recycles vitamin K – which is involved in blood coagulation (clotting). In so doing, the clotting process is destroyed and rodents essentially bleed to death.

The breakthrough for researchers has been the use of gene sequencing to discover mutations in the gene that encodes the VKORC1 enzyme, which is responsible for recycling vitamin K and is the target for anticoagulant rodenticides. These mutations enable rodents to recycle vitamin K in the presence of anticoagulants, thus making them resistant to rodenticides, including many second-generation rodenticides. “Now we have a molecular basis for rodenticide resistance,” said Cornish. “If you can deploy gene sequencing as a tool to understand rodent populations, that really does complete the whole story and allows us to understand what’s happening in the field.”

With this knowledge, the actual tracking of resistant rodents is relatively easy, Cornish said. “You take a piece of tail, send it to a lab, extract the DNA, amplify the VKORC1 gene, sequence it, and see if there is a mutation or not. The type of mutation assists with understanding likely rodenticide performance in the field.”

Syngenta recently collaborated on field trials in Germany as part of the Rodenticide Resistance Action Committee (RRAC). In the RRAC trials, two widely used second-generation anticoagulants were used to treat two German farms infested with rats carrying a known VKORC1 resistance mutation. Since Syngenta’s brodifacoum rodenticide was not part of this RRAC study, Syngenta performed its own field trials on the same resistant rat populations. Syngenta’s brodifacoum product achieved near complete control. Cornish said Syngenta has been fortunate that rodents, thus far, have not shown resistance to brodifacoum in modern studies, but he added that the company is researching different modes of action, in the event that rodents do start showing resistance to brodifacoum.

Syngenta also has been involved in outreach efforts to educate end-users; it is a member of CRRU (the Campaign for Responsible Rodenticide Use), which “aims to protect wildlife while promoting and providing effective rodent control through the responsible use of rodenticides in rural areas.” One of CRRU’s training programs involves educating pest management professionals about resistance and the proper use of rodenticides. “The goal is to develop a strategy, and if you have a product that is not working effectively — especially over a long period of time — don’t use it. That’s what’s going to cause resistance — using a suboptimal product suboptimally,” Cornish said.

How big of a problem is rodenticide resistance in the U.S.? It certainly is not a subject widely discussed. Pat Willenbrock, brand manager for Syngenta, said rodenticide resistance in the U.S., is “under the radar” because (1) many operators are unaware of the problem, whereas it is a recognized issue in Europe; and (2) brodifacoum is more widely used in the U.S.

“I think that some of the research and awareness efforts in Europe are helping, whereas no one here in the U.S. has really done the scientific work,” she said. “We haven’t yet collected the tails here and done the gene sequencing. I don’t know if the typical PMP recognizes that rodenticide resistance exists or that, even if it’s not a big problem now, it could easily become one.”

— Brad Harbison


Song Y., Endepols S., Klemann N., Richter D., Matuschka F.-R., Shi C.-H., Nachman M.W., Kohn M.H. (2011): Adaptive introgression of anticoagulant rodent poison resistance between old world mice. Current Biology 21 (15), 1296-1301. DOI:10.1016/j.cub.2011.06.043.

All photos are courtesy of Dr. Stefan Endepols.

The author is partner of B Communications, www.b-communications.com, an integrated communications/marketing firm specializing in the needs of pest management professionals. He can be reached at jfenner@giemedia.com.