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.

Association of Melanophilin (MLPH) gene polymorphism with coat colour in Rex rabbits

“…In the present study, we sequenced 1689 bp of the entire CDS region of the Rex rabbit MLPH gene, and 13 SNPs were found in 15 exons. Lehner et al (2013) found that, in both colour diluted rabbits (Netherland Dwarf and Loh), the skipping of exons 3 and 4 was present. This resulted in altered amino acids at p.QGL (Reed, 1989;Krawczak et al, 1992;Roscigno et al, 1993) QWA and a premature stop codon at p.K40*.…”

Analysis of genome DNA methylation at inherited coat-color dilutions of Rex Rabbits

“…A number of genes have been found in this study with different splices involved in hair color dilution. A strongly truncated protein caused by an MLPH splice variant leads to a form of hair color dilution in rabbits [35]. The deletion of SLC7A11 in the region from the 11th intron to the adjacent Pcdh18 gene, which changes the amino acid sequence, reduces the formation of melanin, and thus affects coat color [36].…”

Genetic background of coat colour in sheep

“…The MLPH gene codes for melanophilin. The MLPH gene polymorphism is associated with the "diluted" phenotype of many animal species, including cats (Ishida et al, 2006), dogs (Philipp et al, 2005), and rabbits (Lehner et al, 2013). The MATP gene encodes for the Membrane Associated Transporter Protein (MATP), also known as the solute carrier family 45 member 2 (SLC45A2).…”