The rough fur (ruf) mutation in mice is an allele of myelin protein zero-like 3 (Mpzl3)

Background: The recessive rough fur mutation (ruf)―named for the unkempt, greasy appearance of the hair coat in homozygotes―has previously been mapped on mouse Chromosome 9. However, the assignment of ruf to a particular gene is needed to facilitate a complete molecular analysis of the mutant phenotype. Results: To establish a more refined location for ruf (as a basis for positional cloning) DNA isolated from a large backcross family was typed for microsatellite and single-nucleotide markers on Chromosome 9. This analysis restricted the location of ruf between sites that flank only four genes known to be expressed in skin, one of which―Mpzl3, for myelin protein zero-like 3―generates a similar hair phenotype in mice homozygous for engineered and spontaneous null-alleles. A cross between ruf mutants and mice heterozygous for the Mpzl3^rc mutation (which controls a recessive phenotype called rough coat) produced offspring that displayed matted, damp-looking fur, indicating that ruf is a mutant allele of Mpzl3. However, sequence analysis of the Mpzl3 promoter, exons and splice junctions revealed no mutant-specific DNA defect. Conclusion: The results presented indicate that ruf is a mutant allele of Mpzl3. With a genetic assignment in hand, the rough fur variant can now be more fully characterized to advance our understanding of Mpzl3’s role in normal skin development and function, hepatic triglyceride synthesis, weight regulation, energy and glucose homeostasis; and to model-related human disorders.