The “nude” gene discovery in humans
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  • The “nude” gene discovery in humans

  • The “nude” gene discovery in humans

    Dr Angela Christiano and colleagues at the University of Columbia in New York have identified a new gene that causes a rare hair loss disease. This discovery follows on from the research group’s identification of the “hairless” gene in humans in March 1998. The “nude” gene research was published in the Journal Nature on April 8th 1999 and presented at the Society for Investigative Dermatology annual conference in Chicago, May 1999.

    The nude gene has been known about for over 25 years. It was first identified in a strain of mice called “nude” mice (see picture). In the scientific world the gene itself is not actually called nude, it is called whn which is an abbreviation for “winged-helix-nude”. These mice have several things wrong with them. They have little or no hair and they are immunodeficient. The nude gene inhibits the maturation of immune T-cells in the mouse thymus gland, disabling immune function, as well as hair growth. These mice cannot mount a proper immune response to infectious agents and they have to be cared for in special isolated breeding facilities where they can be better protected from disease. Finding the human gene equivalent of these nude mice has been difficult. This is probably because most humans that have the gene mutation die soon after birth due to their immunodeficiency and inability to fight viral or bacterial infections.

    The Columbia University research group used similar methods to those they employed to find the hairless gene in humans. The research group first identified a family from a small village in southern Italy in which two sisters were immunodeficient and had no hair growth. Sadly, one girl died as a result of her immunodeficiency, but the other was given a bone marrow transplant from a family member. The bone marrow graft was successful in giving the young girl a fully immunocompetent immune system able to fight off infection. However, the girl did not have hair regrowth.

    The research group already knew the DNA sequence that coded for the nude gene found in mice. Dr Christiano and friends took this sequence and compared it to DNA taken from the young Italian girl. They discovered the human equivalent of the nude mouse gene on human chromosome 17. The girl carried a mutation in the middle of the nude gene that renders the gene activity ineffective.

    The next step will be for the research group to try and introduce the normal nude gene by topical application of the functional gene sequence to the girl’s scalp. Hopefully the introduction of the new gene will correct the mutation in hair follicles calls and may allow hair to start growing again.

    After announcing her latest discovery Dr Angela Christiano said; "Understanding the genetic underpinnings of the hair cycle will provide much better and rationally designed targets for the treatment of male-pattern baldness and other hair loss disorders in the future." The researchers believe they are moving closer to identifying more genes that control hair follicles and hair growth and this will ultimately lead to potential gene therapies aimed at treating baldness.

    Dr Christiano continues with zeal to identify single gene mutations involved in hair loss diseases. Identifying genes that are irrefutably active in hair follicles is a big step forward in our understanding of hair cycles and growth. This research will help us better understand the activity and functions of different cells in hair follicles and suggest ways that we could intervene with gene therapy to manipulate hair follicle activity.

    Both “nude” and “hairless” diseases are caused by single gene mutations. The common hair loss diseases, androgenetic alopecia and alopecia areata, involve multiple susceptibility genes and they are not purely genetic diseases. Environmental factors can also contribute to the rate, or extent, of hair loss. Finding the genes involved in these types of hair loss disease will be much more difficult. It may be more difficult to find an effective single gene therapy for these diseases polygenic diseases because no single gene is the key to hair loss. It may be that androgenetic alopecia, alopecia areata, and other hair loss diseases will have to be treated with gene therapy that involves transfecting several genes into hair follicles at the same time to create an effective result.

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