Achievement Unlocked : Cow gene study shows why most clones fail

​Dolly was a female domestic sheep, the first mammal to be cloned from an adult somatic cell using the process of nuclear transfer. There are many advantages of a cloned animal. Cloning cattle is an agriculturally important technology and can be used to study mammalian development, but the success rate remains low, with typically fewer than 10 percent of the cloned animals surviving to birth. 

A flowchart showing the process of animal cloning

Harris Lewin, professor in the UC Davis Department of Evolution and Ecology, and colleagues in France and the U.S. used RNA sequencing to look at gene expression in cloned cows during implantation in order to get a better understanding of the molecular mechanisms that lead to a high rate of pregnancy failure for clones. The study is the culmination of 12 years of collaboration and combines the French team’s expertise in cloning and reproductive biology with the U.S. team’s expertise in functional genomics.

The researchers studied tissue from cloned cow embryos — all derived from the same cell line — at 18 and 34 days of development, as well as the corresponding endometrial lining of the pregnant cows. 
The study revealed the points of potential failure for the clones:

1. Problems with hormonal signaling between the developing cloned embryo and the pregnant cow.The study found down-regulation of genes involved in interferon tau, the major signal of pregnancy recognition.

2. The clones also appeared to have an effect on the gene expression of the pregnant cows themselves; on day 34, some uterus tissue showed grossly different gene expression, which could affect the placenta. The interactions between the uterus and the extra-embryonic tissues is critical during implantation.
3.When they compared the results to the Mouse Genomic Informatics Knockout database they found 123 genes that corresponded with functional annotation of abnormal extra-embryonic tissue morphology, 121 associated with embryonic lethality, and 14 with abnormal embryo implantation.

All of the above reasons attributed to the majority of losses that are due to embryonic death, a failure during the implantation process, or the development of a defective placenta.

Dot and Ditto, two healthy cloned calves born at UC Davis in 2003.

Cloning cattle is an agriculturally important technique for mammalian development. This study is for sure going to be the foundation of the future of cattle cloning 

This work has tackled fundamental questions relating to the cloning process.Also it has resulted in the redefinition of understanding of how nuclear reprogramming affects gene expression in extraembryonic tissues of cloned cattle embryos, and the exquisite communication between clones and their recipient mothers.

The research has also provide new insights on how events taking place at implantation drive the progression of pregnancy and shape the post-natal phenotype of the progeny, in cattle as well as in other mammalian species.

Source : Science Daily

Edited by : Siddhi Rao

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