Splashed White (MITF, PAX3)
In horses, there is a broad variety of white spotting patterns. Many mutations in various genes are responsible for a wide variety of patterns. Splashed White (SW) is one type of white spotting. SW-variants have their origin in mutations in the MITF and PAX3 genes. The microphthalmia-associated transcription factor (MITF) gene encodes the MITF-protein, crucial for normal pigment cell function. MITF activates genes involved in pigment production, including those regulating melanocyte proliferation and migration. The paired box gene 3 (PAX3) gene is essential for proper development of some nerve tissue and pigment cells. Dysfunctions is those genes can lead to a different pigment expression.
This article is focused on MITF and PAX mutations (SW-mutations), other variants (like TRMP1 and KIT mutations) are described elsewhere. There are many variants of splashed white. Most of these mutations have only recently emerged and can only be found in specific breeds. Others have a more ancient history.
Clinical features
Some of the SW mutations are homozygous lethal, meaning that homozygous animals are not viable. Some combinations with other white spotting alleles can be unviable as well. Genetic testing can be useful to avoid risky combinations. It’s important to note that the lethal SW-foals are not related to the Lethal White Foal Syndrome (LWS, OLWS, LWO or OLWSF), a homozygous lethal genotype resulting from animals that carry two copies of the LWO allele in the EDNRB gene.
Splashed white has been associated with a higher risk of deafness, especially in animals with al lot of white. Although healthy splashed white horses with a lot of white exist, white horses are known to have more developmental problems. The exact cause is yet unknown but a lot of genes that have a function in pigmentation also have a developmental function.
The splashed white variants show a similar white pattern. Often the head and legs are (mostly) white with blue eyes and sometimes white spots around the belly area. In general, homozygous horses show more white than heterozygous. Combinations with other white patterns (sabino 1, white spotting, overo) exist and although not every combination is viable, those horses also show a higher degree of whiteness than heterozygous horses. Combinations of different (mutant) alleles of the same locus are called compound heterozygotes.
SW1 (MITF)
SW1 is the most prevalent SW-variant. It has been found in many breeds like: American Quarter Horses, Miniature Horses, Islandic Horses, Welsh ponies, Shetland ponies, Arabian horses, Trakehners, Appaloosa Horses, Warmbloods and American Paint Horses. It inherits in an autosomal incomplete dominant manner and homozygotes are viable. Homozygotes usually have more white than heterozygotes.
SB2 (PAX3)
The SW2 or SB2 mutation is a missense mutation in the PAX3 gene. SW2 has been found in homozygous state but these horses likely have a high risk of deafness. SW2 is relatively rare and has only been discovered in American Quarter Horses, American Paint Horses, Lipizzaners and Norikers.
SB3 (MITF)
The SW3 variant is very rare and has only been found in American Quarter Horses and American Paint Horses. Homozygote SW3 horses have not been reported and this variant may be lethal in an early embryotic stage.
Inheritance
All Splashed White variants are autosomal incomplete dominant. In the table below the splashed white (SW) allele has been generalised to SW* so that every variant can be used instead. SW** is a way to mark a different, second variant then the used SW* variant.
| Genotype | Example | Possible Coat Colour | Description |
|---|---|---|---|
| N/N | N/N | No Splashed White pattern. | Splashed white pattern not present. Offspring can only inherit the N allele. |
| N/SW* | N/SW1
N/SW2 N/SW3 |
Horse is a carrier of a dominant white allele and because of the dominant inheritance, the pattern is visible.
Depending on the variant, the whitening may be slight or may cover nearly the entire body |
The horse is carrier of a SW-variant and can either pass on the N or the SW* allele. |
| W*/W* | N/SW1
N/SW2 N/SW3 |
Some variants are homozygous lethal (SW3) so their homozygous coat colour is not known/does not exist.
Often homozygous animals express more white than their heterozygous counterparts. |
Homozygous animals are lethal in some variants and therefore some homozygous genotypes do not occur.
Other variants are viable, in those case the SW* allele is allways passed to their offspring. |
| SW*/SW** SW*/W* SW*/other(fully written as: N/SW* + N/SW**) |
SW1/SW3 SW2/SW* SW2/SB1(fully written as: N/SW* + N/SW**) |
Not all combinations are observed and in these cases effects are unknown.
Often compound heterozygotes express more white than their normal heterozygous counterparts. |
Some combinations of different splashed white alleles are possible, others are lethal.
For both variants it can independently pass on the N allele or de mutant (SW* and other variant) allele. |
Additional information
It’s important to note that in everyday usage, the term splashed white is often used as an umbrella term to mark white colouring in a horse. Scientifically splashed white is a type of whitening that has its origin in specific genes; MITF and PAX3. Be aware to test for the right variant when ordering a white pattern test. Because some homozygous variants and combinations of variants are lethal, knowing the genotype of both parents can be essential to produce a healthy foal.
Relevant tests
- P512
- P513
- P514
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- American Miniature Horse, American Paint Horse, American Quarter Horse, Appaloosa, Icelandic Horse, Miniature Horse, Morgan, Old-Tori, Shetland Pony, Trakehner
- MITF
- Integumentary system
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- American Quarter Horse, Lipizzaner, Noriker
- PAX3
- Integumentary system
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- American Quarter Horse
- MITF
- Integumentary system
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- All breeds
- Multiple systems