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Mice who have genetic material from two fathers but nary a mother

16 January 2013, 08:39

Scientists have created mice that are the genetic product of two fathers, the latest in a series of unusual experiments in mammalian reproduction. Researchers at University of Texas M.D. Anderson Cancer Center and elsewhere first engineered a female mouse whose eggs contained the DNA from a male.

When the female was mated with another male, the offspring had genetic contributions entirely from two males. The study appears online in the peer-reviewed journal Biology of Reproduction.   While the achievement is technically intriguing, its practical benefits are far from clear. Any move to try the same experiment in people is certain to be more complicated and controversial.

The study describes the technique as “a new form of mammalian reproduction” that could potentially be used to improve livestock breeds or preserve endangered species. More provocatively, the authors argue that if certain technical hurdles can be overcome, “then some day two men could produce their own genetic sons and daughters.” But those technical hurdles are extremely high.

“It has been a weird project, but we wanted to see if it could be done” in mice, says Richard Behringer, lead author of the study and a developmental geneticist at M.D. Anderson in Houston.   New techniques are allowing scientists to tweak the biology of reproduction in unusual ways. In April, scientists at U.K.’s Newcastle University created embryos with DNA taken from a man and two women.

The research, published in the journal Nature, was undertaken to potentially help mothers avoid passing on rare genetic disorders to their children. The embryos weren’t brought to term. In 2009, a cloning-related method was used to produce monkeys with genetic material from two mothers.   So how is it possible to engineer mice whose genetic material is entirely from two males?  A human embryo has 46 chromosomes, including two that determine sex.

Females normally have two of the same, written as XX, while males have an X and a Y chromosome, or XY.   In the latest experiment, Dr. Behringer and his colleagues first took a cell from a male mouse—Dad A. They reprogrammed the cell so it became similar to an embryonic stem cell, which eventually gives rise to all the tissues of the body. When copies of the cell were grown in a cell line, about 1% spontaneously lost the Y chromosome, an occurrence that happens when mistakes creep in during cell division.

These cells—with Dad A’s original X chromosome but not the Y chromosome—were injected into blastocysts, early-stage embryos created from donor egg and sperm. The treated blastocysts then were transferred into surrogate mothers.   When the mouse babies were born, they had cells from both the blastocyst and from Dad A—so-called chimeras, which are creatures composed of at least two genetically distinct types of cells. When the females matured, some produced eggs containing only Dad A’s genetic material.

As a final step, the female chimeras mated with an ordinary male mouse, Dad B. Some of the resulting progeny, both male and female, were made entirely from the genetic material originating in the two dads.   One hitch was that, as part of the reprogramming step, the researchers added certain genes that triggered tumors in some mice, an inherent problem in the current approach used for cell reprogramming.  

Trying this in humans is a much bigger challenge. When a human embryo inherits only one X chromosome (instead of one chromosome from each parent) it tends to die. Rarely, females are born this way, called Turner syndrome, and all are infertile. And scientists would also have to find a way to create eggs without creating human chimeras, which is ethically contentious.

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