Categories: Pigmentation phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Disease-related: yes

Key variant known: no

Species-specific symbol: En

Species-specific description: Also known as Dominant White Spotting. For a through summary of early literature, see Robinson (1958, p. 263-265).

Inheritance: As summarised by Fontanesi et al. (2014), who provided additional segregation data that supported single-locus inheritance, "Rabbits homozygous for the recessive non-mutated allele (en/en) are self-colored (not spotted). Heterozygous En/en rabbits are normally spotted and possess far larger patches of colored fur compared to the homozygous En/En animals that have a reduced spotted pattern".

Markers: Noting that mutations in the KIT gene are causative of white spotting in a range of species (cattle, OMIA 001576-9913, OMIA 000209-9913; horse, OMIA 000209-9796; pig, OMIA 000209-9825, OMIA 001745-9825; arctic fox, OMIA 000209-494514; dog, OMIA 001737-9615), Fontanesi et al. (2014) investigated KIT as a candidate gene for English (Dominant White) Spotting in rabbits. A SNP in the rabbit KIT gene that segregated perfectly with the English Spotting phenotypes provided strong evidence that KIT is the causal gene, a conclusion that was supported by immunohistochemical and electron microscopy data, and by KIT expression in the cecum of En/En homozygotes being only 11% of the level in en/en homozygotes. However, the authors were not able to find a causal variant within the KIT gene. Demars et al. (2022) "determined the recessive inheritance of the English spotting phenotype likely involving a copy number variation affecting at least the end of the coding sequence of the KIT gene".

Molecular basis: Because this coat-colour locus is associated with megacolon (see Clinical features), Fontanesi et al. (2010) investigated EDNRB as a comparative functional candidate gene, because mutations in this gene give rise to megacolon in horse (OMIA 000629-9796) and human (OMIM 600155). However, they were able to rule out EDNRB as the causative gene for this trait in rabbits.

Clinical features: As summarised by Fontanesi et al. (2014) "En/En rabbits are subvital compared to vital heterozygous En/en rabbits because dominant homozygous animals are affected by an underlying megacolon" (Robinson, 1958; Bodeker et al., 1995; Wieberneit and Wegner, 1995)