They condensed all the genetic information normally found on a mouse’s Y chromosome to just two genes.
Their study, in the journal Science, showed the male mice could still father babies, albeit needing advanced IVF.
The team in Hawaii argues that the findings could one day help infertile men with a damaged Y chromosome.
DNA is bundled into chromosomes.
In most mammals, including humans, one pair act as the sex chromosomes.
Inherit an X and Y from your parents and you turn out male, get a pair of Xs and the result is female.
Two genes ‘enough’
“The Y chromosome is a symbol of maleness,” lead researcher Professor Monika Ward told the BBC.
In mice, the Y chromosome normally contains 14 distinct genes, with some present in up to a hundred copies.
The team at the University of Hawaii showed that genetically modified mice with a Y chromosome consisting of just two genes would develop normally and could even have babies of their own.
Prof Ward commented: “These mice are normally infertile, but we show it is possible to get live offspring when the Y chromosome is limited to just two genes by using assisted reproduction.”
The mice could only produce rudimentary sperm. But they could have offspring with the help of an advanced form of IVF, called round spermatid injection, which involves injecting genetic information from the early sperm into an egg.
The resulting pups were healthy and lived a normal lifespan.
Reproduction still possible
The two necessary genes were Sry, which kick-starts the process of producing a male as an embryo develops, and Eif2s3y, which is involved in the first steps of sperm production.
However, Prof Ward argues it “may be possible to eliminate the Y chromosome” if the role of these genes could be reproduced in a different way, but added a world without men would be “crazy” and “science fiction”.
“But on a practical level it shows that after large deletions of the Y chromosome it is still possible to reproduce, which potentially gives hope to men with these large deletions,” she added.
The genes which were discarded are likely to be involved in the production of healthy sperm.
Dr Chris Tyler-Smith, from the Wellcome Trust Sanger Institute, said: “This is a great step forward in understanding basic biology.
“But it is important to bear in mind that other mouse Y genes are needed for natural reproduction in mice and as the authors carefully emphasise, the conclusions cannot be applied directly to humans because humans don’t have a direct equivalent of one of the key genes.”
Dr Allan Pacey, a senior lecturer in andrology at the University of Sheffield, said: “This is a very interesting paper, trying to both unravel the genes responsible for sperm production and also shed light on the function of the Y-chromosome.
“The experiments are elegant and seem to show that in the mouse sperm production can be achieved when only two genes from the Y-chromosomes are present.
“Whilst this is of limited use in understanding human fertility, this kind of work is important if we are to unravel to complexities of how genes control fertility.”