OMIA:001597-9986 : Coat colour, English spotting in Oryctolagus cuniculus (rabbit)

Categories: Pigmentation phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: 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)

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001597-9986: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2022 Demars, J., Labrune, Y., Iannuccelli, N., Deshayes, A., Leroux, S., Gilbert, H., Aymard, P., Benitez, F., Riquet, J. :
A genome-wide epistatic network underlies the molecular architecture of continuous color variation of body extremities. Genomics 114:110361, 2022. Pubmed reference: 35378242. DOI: 10.1016/j.ygeno.2022.110361.
2021 Derks, M.F.L., Steensma, M. :
Review: Balancing selection for deleterious alleles in livestock. Front Genet 12:761728, 2021. Pubmed reference: 34925454. DOI: 10.3389/fgene.2021.761728.
Dorożyńska, K., Maj, D. :
Rabbits - their domestication and molecular genetics of hair coat development and quality. Anim Genet 52:10-20, 2021. Pubmed reference: 33216407. DOI: 10.1111/age.13024.
2014 Fontanesi, L., Vargiolu, M., Scotti, E., Latorre, R., Faussone Pellegrini, M.S., Mazzoni, M., Asti, M., Chiocchetti, R., Romeo, G., Clavenzani, P., De Giorgio, R. :
The KIT gene is associated with the english spotting coat color locus and congenital megacolon in Checkered Giant rabbits (Oryctolagus cuniculus). PLoS One 9:e93750, 2014. Pubmed reference: 24736498. DOI: 10.1371/journal.pone.0093750.
2010 Fontanesi, L., Vargiolu, M., Scotti, E., Mazzoni, M., Clavenzani, P., De Giorgio, R., Romeo, G., Russo, V. :
Endothelin receptor B (EDNRB) is not the causative gene of the English spotting locus in the domestic rabbit (Oryctolagus cuniculus). Anim Genet 41:669-70, 2010. Pubmed reference: 20497153. DOI: 10.1111/j.1365-2052.2010.02084.x.
1995 Bodeker, D., Turck, O., Loven, E., Wieberneit, D., Wegner, W. :
Pathophysiological and functional aspects of the megacolon-syndrome of homozygous spotted rabbits Zentralbl Veterinarmed A 42:549-59, 1995. Pubmed reference: 8822192. DOI: 10.1111/j.1439-0442.1995.tb00410.x.
Wieberneit, D., Wegner, W. :
Albino rabbits can suffer from Megacolon-Syndrome when they are homozygous for the “English-spot” gene (En En). World Rabbit Science 3:19-26, 1995.
1994 Flemming, K., Kühnel, C., Wieberneit, D., Wegner, W. :
[The problems of spotted breeds of rabbits. 4. Morpho- and histometric findings in the CNS and thyroid glands and the hormone content in blood at slaughter of hybrid rabbits, and estimation of the heterosis effect]. Dtsch Tierarztl Wochenschr 101:434-9, 1994. Pubmed reference: 7895623.
1993 Gerlitz, S., Wessel, G., Wieberneit, D., Wegner, W. :
[The problems of breeding spotted rabbits. 3. Variability of the pigmentation grade, ganglionic intestinal wall supply, relationship to pathogenesis--animal breeding and animal welfare aspects]. Dtsch Tierarztl Wochenschr 100:237-9, 1993. Pubmed reference: 8339710.
1992 Mahdi, N., Wieberneit, D., Wegner, W. :
[The problem of breeding for spots in rabbits. 2. Further results on the variation of characteristics in fattening and breeding animals]. Dtsch Tierarztl Wochenschr 99:111-3, 1992. Pubmed reference: 1576947.
1991 Wieberneit, D., Mahdi, N., Zacharias, K., Wegner, W. :
[The problems of spotted breeds of rabbits. 1. Fattening and body condition at slaughter, organ parameters]. Dtsch Tierarztl Wochenschr 98:352-4, 1991. Pubmed reference: 1954863.
1958 Robinson, R. :
Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.
1954 Rifaat, O.M. :
White spotting in mice and rabbits. Genetica 27:286-92, 1954. Pubmed reference: 14366219.
1924 Castle, W.E. :
Linkage of Dutch, English, and Angora in Rabbits. Proc Natl Acad Sci U S A 10:107-8, 1924. Pubmed reference: 16576789. DOI: 10.1073/pnas.10.3.107.

Edit History

  • Created by Frank Nicholas on 31 Aug 2011
  • Changed by Frank Nicholas on 31 Aug 2011
  • Changed by Frank Nicholas on 07 Sep 2011
  • Changed by Frank Nicholas on 03 May 2014
  • Changed by Frank Nicholas on 06 May 2014
  • Changed by Frank Nicholas on 29 Apr 2016
  • Changed by Imke Tammen2 on 18 Jan 2022
  • Changed by Frank Nicholas on 28 Oct 2022