title: The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8).
abstract: Please cite this paper as: The mouse frizzy (fr) and rat 'hairless' (fr(CR)) mutations are natural variants of protease serine S1 family member 8 (Prss8). Experimental Dermatology 2010; 19: 527-532. Abstract: We have previously suggested (based on genetic mapping analysis) that the allelic 'fuzzy' and 'hairless' mutations in the rat are likely orthologues of the mouse frizzy mutation (fr). Here, we analysed three large intraspecific backcross panels that segregated for mouse fr to restrict this locus to a 0.6-Mb region that includes fewer than 30 genes. DNA sequencing of one of these candidates known to be expressed in skin, protease serine S1 family member 8 (Prss8), revealed a T to A transversion associated with the fr allele that would result in a valine to aspartate substitution at residue 170 in the gene product. To test whether this missense mutation might be the molecular basis of this frizzy variant, we crossed fr/fr mice with mice that carried a recessive perinatal lethal mutation in Prss8. Hybrid offspring that inherited both fr and the Prss8 null allele displayed abnormal hair and skin, showing that these two mutations are allelic, and suggesting strongly that the T to A mutation in Prss8 is responsible for the mutant frizzy phenotype. Sequence analysis of all Prss8 coding regions in the 'hairless' rat identified a 12-bp deletion in the third exon, indicating that mouse fr and the rat 'hairless' mutations are indeed orthologues. However, this analysis failed to detect any alterations to Prss8 coding sequences in the allelic 'fuzzy' rat variant.
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, New Britain, CT, USA.
authors.forename: Damek V
authors.initials: DV
authors.lastname: Spacek
authors.forename: Amarilis F
authors.initials: AF
authors.lastname: Perez
authors.forename: Katelynn M
authors.initials: KM
authors.lastname: Ferranti
authors.forename: Lillya K-L
authors.initials: LK
authors.lastname: Wu
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moy
authors.forename: David R
authors.initials: DR
authors.lastname: Magnan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: King
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics; D005260:Female; D005816:Genetic Complementation Test; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D018859:Hair Follicle / Q000473:pathology; D007178:Inbreeding; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051381:Rats; D054772:Rats, Hairless; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics*; D012867:Skin / Q000473:pathology; D014738:Vibrissae / Q000473:pathology; D000099271:Prostasin
chemical_list: D012697:Serine Endopeptidases; D000099271:Prostasin