Scientists record cloning breakthrough

Japanese bi­ol­o­gists say they’ve cre­at­ed nor­mal, healthy mouse clones with a new tech­nique that can pro­duce cop­ies of cop­ies, and so on, with no ap­par­ent lim­it.

The new meth­od seems to sweep aside bar­ri­ers to safe, ef­fi­cient cloning, said the re­search­ers. They used a var­i­ant of the tech­nique that in 1996 led to the first mam­mal cloned from an adult cell, Dolly the sheep. The pro­ce­dure, called so­mat­ic cell nu­clear trans­fer, in­volves put­ting a cell nu­cle­us con­tain­ing the ge­net­ic in­forma­t­ion of the crea­ture to be cloned, in­to a liv­ing egg with its own nu­cle­us re­moved.

Sci­en­tists have pre­vi­ously strug­gled with low suc­cess rates and lim­its on how many times mam­mals could be re­cloned. At­tempts at re­clon­ing cats, pigs and mice more than two to six times had failed.

 

 

In the new work, Teru­hiko Wa­ka­ya­ma at the RIKEN Cen­ter for De­vel­op­men­tal Bi­ol­o­gy in Ko­be, Ja­pan, led a team that tweaked the tech­nique to make 581 clones of one orig­i­nal mouse through 25 con­sec­u­tive rounds of cloning. There was no vis­i­ble drop in the suc­cess rate, the re­search­ers said, re­port­ing their find­ings March 7 in the jour­nal Cell Stem Cell.

“One pos­si­ble ex­plana­t­ion for this [past] lim­it on the num­ber of re­clon­ing at­tempts,” Wa­ka­ya­ma said, “is an ac­cu­mula­t­ion of ge­net­ic or ‘epige­net­ic’ abnor­mal­i­ties” over genera­t­ions. Epige­net­ic changes are al­tera­t­ions to DNA func­tion that don’t in­volve a change in the DNA code it­self.

To pre­vent these aberra­t­ions, Wa­ka­ya­ma and his team added a sub­stance called tri­cho­statin to the cell cul­ture me­di­um used for the pro­cess. Tri­cho­statin is a his­tone de­acety­lase in­hib­i­tor, a com­pound that pre­vents chem­i­cal changes to DNA-associated struc­tures called his­tones. These changes in turn can cause epi­ge­net­ic abnor­mal­i­ties by af­fect­ing the way DNA is “pack­aged.”

Wa­ka­ya­ma and col­leagues said they in­creased cloning ef­fi­cien­cy by up to six­fold and im­proved each step of the pro­ce­dure. The 581 mice ob­tained through se­quen­tial cloning were all healthy, fer­tile, gave birth to healthy pups and lived about two years, like nor­mal mice, the sci­en­tists said.

“Our re­sults show that there were no ac­cu­mula­t­ions of epige­net­ic or ge­net­ic abnor­mal­i­ties in the mice, even af­ter re­peat­ed cloning,” wrote the au­thors. “This tech­nique could be very use­ful for the large-scale pro­duc­tion of superior-qual­ity an­i­mals, for farm­ing or con­serva­t­ion pur­pos­es,” added Wa­ka­ya­ma, who al­so made the news in 2008 when his team cre­at­ed clones from the bod­ies of mice fro­zen for 16 years.

.Courtesy of the RIKEN Center for Developmental Biology and World Science staff

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