Friday, November 24, 2017

Clearing Dolly: Radiographs of taxidermied sheep clone's remains investigate osteoarthritis, aging

We were warned. Almost 20 years ago, skeptics and opponents of the cloning of horses and other livestock forecast musculoskeletal calamities and weaknesses. It seemed like the prophecies of doom had come true back in 2003, when reports circulated that Dolly, the famous (and first) ewe cloned  in 1996, suffered from what might be considered premature aging, in the form of osteoarthritis (OA).

Now, researchers in the United Kingdom are about to clear Dolly's name and show additional evidence of normal aging in the tribe of university-cloned sheep that followed her.

Reports in 2003 that Dolly, the first animal cloned from adult cells, was suffering from osteoarthritis at the age of 5½ led to considerable scientific concern and media debate over the possibility of early-onset age-related diseases in cloned animals.

Dolly, the world's first cloned mammal from an adult cell, is on display at the National Museums of Scotland in Edinburgh. (Creative Commons file image via Wikimedia)

However, the only formal record of OA in the original Dolly was a brief mention in a conference abstract; it reported that Dolly had OA of the left knee. In the absence of the original records two research teams decided to find out for themselves whether the concerns were justified.

Researchers to the rescue

Teams at the University of Nottingham in England and the University of Glasgow in Scotland published research last year showing that a group of eight-year-old Nottingham ‘Dollies’ had aged normally. Last week, they published further evidence, in the form of a radiographic assessment of the skeletons of Dolly herself, Bonnie (her naturally conceived daughter) and Megan and Morag (the first two animals to be cloned from differentiated cells).

Their article, Radiographic assessment of the skeletons of Dolly and other clones finds no abnormal osteoarthritis, has been published in the online Nature Research Open Access journal Scientific Reports. They show that the skeletons, stored in the collections of National Museums of Scotland in Edinburgh, display radiographic OA similar to that observed in naturally-conceived sheep and Nottingham’s healthy aged clones.

Kevin Sinclair, Professor of Developmental Biology, in the School of Biosciences at the University of Nottingham, said: “No formal, comprehensive assessment of osteoarthritis in Dolly was ever undertaken. We therefore felt it necessary to set the record straight.”

Nottingham’s Dolly legacy

The four Nottingham ‘Dollies’ - Debbie, Denise, Dianna and Daisy – were derived from the cell line that gave rise to Dolly. The researchers concluded that the Nottingham Dollies had aged normally with no clinical signs of OA. They had radiographic evidence of only mild or, in one case, moderate OA.

Their results, published July last year in the academic journal Nature Communications, were in apparent stark contrast to Dolly the Sheep’s diagnosis of early onset OA which led to scientific concern and media debate over the possibility of early-onset, age-related diseases in cloned animals.

Radiographic examinations

The researchers travelled to Edinburgh and, with special permission from Dr Andrew Kitchener, Principal Curator of Vertebrates at National Museums Scotland, undertook radiographic examinations of the skeletons of Dolly and her contemporary clones.

Professor Corr said: “We found that the prevalence and distribution of radiographic-OA was similar to that observed in naturally-conceived sheep, and our healthy aged cloned sheep. As a result we conclude that the original concerns that cloning had caused early-onset OA in Dolly were unfounded.”

More about sheep and ageing
Commercially-produced sheep are rarely kept beyond the age of 6-7 years. Their natural life expectancy rarely extends beyond 9-10 years. 

The Nottingham Dollies, who would now be over 10 years of age, have been humanely euthanized but their legacy continues. Professor Sinclair and his team are currently undertaking detailed molecular studies to gain a greater insight into the aging process.

Read the Open Access article:

S. A. Corr, D. S. Gardner, S. Langley-Hobbs, M. G. Ness, A. C. Kitchener, K. D. Sinclair. Radiographic assessment of the skeletons of Dolly and other clones finds no abnormal osteoarthritis. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-15902-8

Materials kindly provided by the University of Nottingham were utilized in the creation of this article.

Background on Dolly:

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