Witch Nails (Krt90whnl): A spontaneous mouse mutation affecting nail growth and development

Area of Science:

• Genetics
• Developmental Biology
• Animal Models

Background:

• Nail deformities in humans and mice often share similarities.
• Understanding the genetic basis of nail development is crucial for identifying disease mechanisms.

Purpose of the Study:

• To characterize a novel spontaneous mouse mutation, witch nails (whnl), affecting nail morphology.
• To identify the genetic cause of the whnl mutation and its impact on the KRT90 protein.
• To evaluate the potential of this mouse model for studying nail and hoof diseases.

Main Methods:

• Phenotypic analysis of homozygous mutant mice.
• Genetic mapping of the whnl mutation to Chromosome 15.
• DNA sequencing to identify mutations in the Krt90 gene.
• Immunohistochemistry to assess KRT90 protein expression.

Main Results:

• The whnl mutation causes degenerative changes in the distal nail matrix and nail bed, leading to long, curved nails.
• A 7-bp insertion in the Krt90 gene (exon 9) results in a frameshift mutation (p. Ser476ArgfsTer36).
• Normal KRT90 protein is expressed in the nail matrix and bed; mutant mice show lesions in these areas.

Conclusions:

• The whnl mutation is the first identified spontaneous mutation in the Krt90 gene, providing insight into nail development pathways.
• The Krt90 gene plays a critical role in regulating nail plate and nail bed formation.
• This mouse model may be valuable for studying equine laminitis and other hoof and nail disorders due to similarities in lesion presentation.