title: The mouse wellhaarig (we) mutations result from defects in epidermal-type transglutaminase 3 (Tgm3).
abstract: The recessive wellhaarig (we) mutations, named for the wavy coat and curly whiskers they generate in homozygotes, have previously been mapped on mouse Chromosome 2. To further limit the possible location of the we locus, we crossed hybrid (C57BL/6×AKR)F1, we(4J)/+ females with AKR, we(4J)/we(4J) mutant males to create a large backcross family that was typed for various microsatellite markers and single-nucleotide polymorphisms (SNPs) that distinguish strains AKR and B6. This analysis restricted the location of we(4J) between sites that flank only one gene known to be expressed in skin: epidermal-type transglutaminase 3 (Tgm3). To test Tgm3 as a candidate for the basis of the wellhaarig phenotype we took two approaches. First, we sequenced all Tgm3 coding regions in mice homozygous for four independent, naturally-occurring wellhaarig alleles (we, we(Bkr), we(3J) and we(4J)) and found distinct defects in three of these mutants. Second, we crossed mice homozygous for an induced mutant allele of Tgm3 (Tgm3(Btlr)) with mice heterozygous for one of the wellhaarig alleles we possess (we(4J) or we(Bkr)) to test for complementation. Because the progeny inheriting both a recessive we allele and a recessive Tgm3(Btlr) allele displayed wavy hair, we conclude that the classic wellhaarig mutations result from defects in Tgm3.
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Brennan
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Minh T
authors.initials: MT
authors.lastname: Huynh
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Rabah
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Hailie E
authors.initials: HE
authors.lastname: Shaw
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Bisaillon
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Legairre A
authors.initials: LA
authors.lastname: Radden
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Tu V
authors.initials: TV
authors.lastname: Nguyen
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA. Electronic address: kingt@ccsu.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: King
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D004817:Epidermis / Q000201:enzymology*; D005260:Female; D005816:Genetic Complementation Test; D006197:Hair; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011503:Transglutaminases / Q000235:genetics*
chemical_list: C498713:Tgm3 protein, mouse; D011503:Transglutaminases
keywords: Complementation testing; Hair morphology; Intraspecific backcross mapping; Positional candidate approach