MLPH (Melanophilin Gene): MLPH is one of three genes responsible for the even distribution of pigment. The others being Rab27a and MyoVa. Therefore, as you might have guessed, mutations in these genes affect the way pigment is distributed. Mutations in MYOVA, RAB27A, and MLPH can cause dilution of the skin, hair, and eyes as well as other abnormalities. In humans this includes the Griscelli syndromes and in mice the dilutions ashen, leaden, and dilution. Mutations in Rab27a and MyoVa tend to be the most severe (although not always) and can cause a range of problems including neurological impairment, immune deficiencies and blood disorders but thankfully mutations in MLPH seem to be the most common and also the least problematic. Mutations in MLPH, Rab27a and MyoVa cause a visual dilution by causing pigment to clump together instead of being evenly distributed along the hair shaft. This is the result of alterations in the pigment transport systems that these genes encode. These mutations result in a dilution of both black and red pigment and also in the dilution of skin and eye color. Mutations in MLPH can result in other abnormalities, such as hair loss and skin inflammation in dogs but more often than not these mutations appear to only include dilution of the skin, hair, and eyes.
Mutations in MLPH are responsibly for a variety of similar phenotypes across mammalian species. On of the most interesting correlations is that the mutation that causes Lavender in chickens is “the exact same mutation” that also causes Griscelli syndrome type 3 in humans. Griscelli Syndrome Type 3 is the least problematic of the 3 Griscelli Syndromes causing only dilution and no other abnormalities. Similar mutations are also responsible for lavender in quail, leaden in mice, silver in mink and of course Dilution in dogs and cats. Dilution is the easiest to recognize in animals that would otherwise be black. It lightens the coat and skin to gray and the eyes to light brown or yellow. In both cats and dogs these black dilutes are often known as “blue”. In animals that are not solid black it results in colorations such as blue and tan (diluted black and tan) in dogs and blue and cream in cats (dilute tortoiseshell). In all known cases mutation in MLPH have resulted in a dilution that is inherited as a recessive. This means that both parents but be a carrier of the mutation for any offspring to be affected. It might be interesting to note that while MLPH mutations appear in humans, chickens, mice, rats, cats, and dogs, no MLPH mutations are known to exist in horses. While Dun, at first glance, may seem to have many similarities, it is inherited as a dominant mutation which would be unusual (although not impossible) in a dilution caused by MLPH gene mutation. MLPH may also be responsible for Dilution in rabbits but this remain to be determined. Several candidate genes have been ruled out as cause for dilution in rabbits but MLPH has not yet been studied.