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Move over, lab mice, there's a new model for studying the human brain.

Genetically engineered ferrets might provide better insight into a condition called microcephaly.

The study, published April 11 in Nature, reveals the first ferret with a neurological mutation.

The mutation occurred in a gene called ASPM, located in the cerebral cortex. In people, mutations in this gene reduce the size of the brain by up to 50%, causing a condition called microcephaly. This condition has been linked to recent outbreaks of the Zika virus.

Typically, laboratory mice are used in the study of microcephaly. However, inactivation of the ASPM gene only shrinks their brains by 10%, providing limited insight into human cortical development.

The ferret has a much more complex brain than the laboratory mice. Although they've been used for neurological research for over 30 years, this is only the second knockout ferret ever created.

"Ferrets breed easily, and have a large cortex with gyri (folds) that are typical of most mammals, but which rodents like mice lack altogether. Also, ferrets have the same range of brain progenitor cell types seen in humans, but mice do not," Christopher Walsh, a Howard Hughes Medical Institute investigator at Boston Children’s Hospital, told ALN.

"Ferrets are typical of other mammals, yet have large litters, breed easily, are surgically accessible, and now we know that they are easy to engineer genetically."

The genetically engineered ferret models created for this research displayed severely shrunken brains, with up to 40% reduced brain weight. Cortical thickness and cell organization were preserved, as seen in humans with microcephaly.

"Ferrets are already an important model in influenza research, because their lungs also resemble humans. But for the brain, there are an array of human diseases that affect a progenitor cell type known as outer radial glial cells,  These cells are thought to be key to the development of autism and certain types of epilepsy, and to be very important to the evolution of the human brain," Walsh said.

"WE intend to study the ASPM mutant ferret further, to better understand the cell types that are affected by the mutation. And we look forward to engineering other mutants in ferrets that will be better models of other human brain developmental disorders."

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