title: Two-exon skipping within MLPH is associated with coat color dilution in rabbits.
abstract: 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.
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lehner
authors.affiliation: Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Gähle
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dierks
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany ; Clinic for Pets, Reptiles and Pet and Feral Birds, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Stelter
authors.affiliation: Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gerber
authors.affiliation: Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Brehm
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ottmar
authors.initials: O
authors.lastname: Distl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D005808:Genes, Recessive; D006200:Hair Color / Q000235:genetics*; D008969:Molecular Sequence Data; D010858:Pigmentation / Q000235:genetics*; D011817:Rabbits / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary