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Chimera (animal)

In zoology, a chimera is an animal which has two or more different populations of cells, which are genetically distinct and which originated in different zygotes (fertilized eggs). It either is acquired through the infusion of allogeneic hematopoietic cells during transplantation or transfusion or it is inherited.

In fraternal twins, chimerism occurs by means of blood-vessel anastomoses. Chimeras are named after the mythological creature Chimera.

Chimeras are formed from either 4 parent cells (2 fertilized eggs or early embryos are fused together) or 3 parent cells (a fertilized egg is fused with an unfertilized egg or a fertilized egg is fused with an extra sperm). Each population of cells keeps its own character and the resulting animal is a mosaic of mis-matched parts.

An analogy is two jigsaw puzzles cut using an identical cutter, but with different pictures. You can make a single puzzle out of the mis-matched parts, but the completed puzzle will show parts of both different pictures. Chimeras can often breed, but the fertility and type of offspring depends on which cell line gave rise to the ovaries or testes.

Tetragametic chimerism

Tetragametic chimerism is a less common cause of congenital chimerism. It occurs through the fertilization of two ova by two spermatozoa, followed by the fusion of the zygotes and the development of an organism with intermingled cell lines. This happens at a very early stage of development, such as that of the blastocyst. Such an organism is called a tetragametic chimera as it is formed from four gametes — two eggs and two sperm.

As the organism develops, the resulting chimera can come to possess organs that have different sets of chromosomes. For example, the chimera may have a liver composed of cells with one set of chromosomes and have a kidney composed of cells with a second set of chromosomes. This has occurred in humans, though it is considered extremely rare.

Affected persons are identified by the finding of two populations of red cells or ambiguous genitalia/intersex syndrome alone or in combination; such persons sometimes also have patchy skin or eye pigmentation. If the blastocysts are of the same sex, it can only be detected through DNA testing, which itself is currently rare, and it may be more common than currently believed. If the blastocysts are of opposite sex, genitals of both sexes are formed, either ovary and testis, or combined ovotestes, in one rare form of intersexuality, a condition previously known as true hermaphroditism. As of 2003, there were about 40 human cases in the literature, according to New Scientist.

Natural chimeras are not detected unless the offspring has abnormalities, such as male/female or hermaphrodite characteristics, also skin discoloring. The most noticeable are some tortoiseshell male cats or animals with ambiguous sex organs or behavioural abnormalities such as confused gender behaviour (where female cells made the brain but male cells made the gonads or vice versa). Recent studies of tortoiseshell male cats and unusually coloured tortoiseshell-like cats suggest that natural chimerism is far more common than previously realised and that it frequently goes undetected.

Chimerism can sometimes be detected in DNA testing. The Lydia Fairchild case, for example, was brought to court after DNA testing showed (mistakenly so !) that her children could not be hers, since DNA didn’t match. The charge against her was dismissed when became clear that Lydia was a chimera, with the matching DNA found in her cervical tissue.

The tetragametic state has important implications for organ or stem-cell transplantation. Chimeras typically have immunologic tolerance to both cell lines. Thus, for a tetragametic human, a wider array of relatives and other persons may be eligible to be organ donors.

Microchimerism

Microchimerism is the presence of a small number of cells, genetically distinct from those of the host individual, and an organ. The most common form is fetomaternal microchimerism (or fetal chimerism) whereby cells from a fetus pass through into the mother. Fetal cells have been documented to persist in maternal circulation for as long as 27 years. Microchimerism had also been shown to exist after blood transfusion to severely immune compromised population of patients who suffered trauma.

Research chimerism

In biological research, chimeras are artificially produced by mixing cells from two different organisms. This can result in the eventual development of an adult animal composed of cells from both donors, which may be of different species — for example, in 1984 a chimeric geep was produced by combining embryos from a goat and a sheep. A chicken with a quail’s brain has been produced by grafting portions of a quail embryo into a chicken embryo.

Interspecies chimeras are made in the laboratory. In addition to the famous geep, there are rat/mouse chimeras and a rabbit/human chimera that was not allowed to develop beyond a few days. Like hybrids, the parent species must be closely enough related in order to produce live offspring that are relatively healthy. Chimeras between different varieties of mice are relatively common in embryology. By fusing cells of differently coloured or otherwise genetically distinct mice, researchers have been able to see how embryos form and which structures are related (arise from which line of cells).

In August 2003, researchers at the Shanghai Second Medical University in China reported that they had successfully fused human skin cells and rabbit eggs to create the first human chimeric embryos. The embryos were allowed to develop for several days in a laboratory setting, then destroyed to harvest the resulting stem cells. Increasingly realizable projects using part-human, part-animal chimeras as living factories for producing cells or organs for xenotransplantation raise a host of ethical and safety issues.

Chimeras should not be confused with hybrids, which are organisms formed from two gametes (each from a different species) which formed a single zygote. All cells in a hybrid originate from this single zygote. For example, a mule is a hybrid created from the sperm of a donkey and the egg of a horse.

Chimeras should also not be confused with mosaics, which are organisms with genetically different cell types, but which again originate from a single zygote.

Chimera Proteins

In April 2005, scientists at the University of California created a chimera protein of a human protein and cat protein. They fused the feline Fel d 1 protein (the protein that triggers an allergic reaction in susceptible people) with a human protein known to suppress allergic reactions. When tested in mice, the chimeric protein stifled cat allergy. The feline part of the protein binds to the specific immune cells that generate the allergic reaction to Fel d 1. The human part of the protein also binds to the immune cells and tells them to stop reacting. Because the human part is more dominant, the allergic reaction is halted. Chimeric proteins could be used to desensitise allergy sufferers by retraining their immune system.

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