Paternal-Free Mice

Posted on May 1, 2004 by Inception Fertility

We occasionally get asked by same sex couples if it is possible to create an embryo, and hence a baby, by using the DNA either from 2 sperm or 2 eggs, instead of the DNA from a sperm and an egg. In mammals, such a feat hasn't been possible until recently. A paper in the scientific journal Nature (22nd April 2004) reports the birth of 2 mice; each created using the DNA from 2 eggs and with no sperm. Creating offspring using only female genes and with no paternal contribution is a common phenomenon in nature and in fact is a method of reproduction employed by almost all plants and animals. Mammals however have not been able to reproduce in this way. This impediment is attributed in large part to a process called genomic imprinting. Experimentally, when mouse embryos are created using only the DNA from 2 eggs, the resulting fetus is well formed, but only a rudimentary placenta develops and the pregnancy fails. This is because the placenta is created mainly by paternal genes, and without the involvement of a sperm, we can't get a normal placenta. But if we have 2 copies of almost every gene (one from Mom and one from Dad), why can't the maternal genes make a placenta? Biologists think that it's a conflict of interest for Mom's genes to make the placenta. Since the placenta in many ways is a parasite that fights for Mom's resources, Mom's placental genes are deliberately inactivated or switched off and it's left to Dad to make the placenta. This process of deliberately inactivating a set of genes from one parent, so that the other parent's genes are left to do the work is called imprinting. These genes carry with them a history of their origin because they are endowed at conception with a maternal or paternal imprint. One negative consequence of imprinting is that when an imprinted gene is defective or otherwise does not work, the inactive, but perfectly good gene from the other parent can't be called upon to help out. Diseases like Prader-Willi syndrome and Angelman's syndrome which have variable physical, mental and behavioral effects on afflicted individuals are caused by defective imprinted genes. So what happens when an embryo is created using 2 sperm and without maternal DNA? In this instance, as would be expected, the placenta is normal and fully formed, but the fetus is typically deformed and most notably lacks a head. It could be said that without a Mom, mammals lose their heads. In the Nature paper, the mice without a father were created after exhaustive attempts: 2 live born from 457 reconstructed eggs. And the researchers used a trick to get around the imprinting issue. To make each embryo they used a mature (ovulated) egg and an immature egg from a newborn mouse in which the genomic imprint had not been established (imprinting occurs as eggs grow and mature). This allowed them to overcome the absence of the paternal imprinted genes since there were few or no imprinted (and therefore inactive) genes in the DNA from the immature eggs. The process was not very efficient in creating live offspring, but one of the resulting mice reproduced normally after reaching adulthood. The second mouse was used in tests to determine its DNA normalcy.

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