title: The retarded hair growth (rhg) mutation in mice is an allele of ornithine aminotransferase (Oat).
abstract: Because of the similar phenotypes they generate and their proximate reported locations on Chromosome 7, we tested the recessive retarded hair growth (rhg) and frizzy (fr) mouse mutations for allelism, but found instead that these defects complement. To discover the molecular basis ofrhg, we analyzed a large intraspecific backcross panel that segregated forrhgand restricted this locus to a 0.9 Mb region that includes fewer than ten genes, only five of which have been reported to be expressed in skin. Complementation testing betweenrhgand a recessive null allele of fibroblast growth factor receptor 2 eliminatedFgfr2as the possible basis of the retarded hair growth phenotype, but DNA sequencing of another of these candidates, ornithine aminotransferase (Oat), revealed a G to C transversion specifically associated with therhgallele that would result in a glycine to alanine substitution at residue 353 of the gene product. To test whether this missense mutation might cause the mutant phenotype, we crossedrhg/rhgmice with mice that carried a recessive, perinatal-lethal, null mutation in Oat (designatedOatΔherein). Hybrid offspring that inherited bothrhgandOatΔdisplayed markedly delayed postnatal growth and hair development, indicating that these two mutations are allelic, and suggesting strongly that the G to C mutation inOatis responsible for the retarded hair growth phenotype. Comparisons among +/+,rhg/+,rhg/rhgandrhg/OatΔmice showed plasma ornithine levels and ornithine aminotransferase activities (in liver lysates) consistent with this assignment. Because histology of 7- and 12-month-oldrhg/rhgandrhg/OatΔretinas revealed chorioretinal degeneration similar to that described previously forOatΔ/OatΔmice, we suggest that therhgmutant may offer an ideal model for gyrate atrophy of the choroid and retina (GACR) in humans, which is also caused by the substitution of glycine 353 in some families.
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: Eric T
authors.initials: ET
authors.lastname: Szabo
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Hughes
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Feliciano
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Alex V
authors.initials: AV
authors.lastname: Nesta
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Petrovic
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Palanza
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Dainius
authors.initials: D
authors.lastname: Lancinskas
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Szmurlo
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Artus
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kapper
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Mulrooney
authors.affiliation: Biomolecular Sciences, Central Connecticut State University, 1615 Stanley Street, New Britain, CT 06053, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: King
keywords: Alopecia; Complementation testing; Gyrate atrophy of the choroid and retina; Intraspecific backcross mapping; Positional candidate approach