Two-exon skipping within MLPH is associated with coat color dilution in rabbits

PLoS One. 2013 Dec 20;8(12):e84525. doi: 10.1371/journal.pone.0084525. eCollection 2013.


Coat color dilution turns black coat color to blue and red color to cream and is a characteristic in many mammalian species. Matings among Netherland Dwarf, Loh, and Lionhead Dwarf rabbits over two generations gave evidence for a monogenic autosomal recessive inheritance of coat colour dilution. Histological analyses showed non-uniformly distributed, large, agglomerating melanin granules in the hair bulbs of coat color diluted rabbits. We sequenced the cDNA of MLPH in two dilute and one black rabbit for polymorphism detection. In both color diluted rabbits, skipping of exons 3 and 4 was present resulting in altered amino acids at p.QGL[37-39]QWA and a premature stop codon at p.K40*. Sequencing of genomic DNA revealed a c.111-5C>A splice acceptor mutation within the polypyrimidine tract of intron 2 within MLPH. This mutation presumably causes skipping of exons 3 and 4. In 14/15 dilute rabbits, the c.111-5C>A mutation was homozygous and in a further dilute rabbit, heterozygous and in combination with a homozygous frame shift mutation within exon 6 (c.585delG). In conclusion, our results demonstrated a colour dilution associated MLPH splice variant causing a strongly truncated protein (p.Q37QfsX4). An involvement of further MLPH-associated mutations needs further investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Alternative Splicing / genetics*
  • Animals
  • Base Sequence
  • Crosses, Genetic
  • DNA, Complementary / genetics
  • Exons / genetics*
  • Frameshift Mutation / genetics
  • Genes, Recessive
  • Hair Color / genetics*
  • Molecular Sequence Data
  • Pigmentation / genetics*
  • Rabbits / genetics*
  • Rabbits / physiology
  • Sequence Analysis, DNA


  • Adaptor Proteins, Signal Transducing
  • DNA, Complementary

Grants and funding

The project has been supported by internal funds of the University of Veterinary Medicine Hannover. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.