The mouse hairy ears mutation exhibits an extended growth (anagen) phase in hair follicles and altered Hoxc gene expression in the ears.
The mouse In(15)2Rl (hairy ears, Eh) mutation is a paracentric inversion of the distal half of chromosome 15 (Chr 15). Heterozygous Eh/+ mice display misshaped and hairy ears that have more and longer hair than the ears of their wild-type littermates. We mapped, cloned and sequenced both inversion breakpoints. No protein-coding transcript was disrupted by either breakpoint. The proximal breakpoint is located between syntrophin basic 1 (Sntb1) and hyaluronan synthase 2 (Has2), and the distal breakpoint maps between homeobox C4 (Hoxc4) and single-strand selective monofunctional uracil DNA glycosylase (Smug1), near the middle and the telomere ends of Chr 15, respectively. The inversion spans ~47 megabases. Our genetic analysis suggests that the hairy-ear phenotype is caused by the proximal breakpoint of the inversion-bearing Chr 15. Quantitative RNA analysis by real-time polymerase chain reaction for the genes flanking the breakpoint indicated no changes in expression levels except for some homeobox C (Hoxc) genes whose expression was elevated in developing and mature skin of the ears but not of other body regions. The increased hair length on the ears of Eh/+ mice was due to an extension of the anagen stage in the hair cycle, as determined by histological analysis. Our data indicate that the Eh phenotype arises from mis-expression of Hoxc genes.
Mentzer
Sarah E
SE
Mammalian Genetics and Genomics Group, Life Sciences Division, Oak Ridge National Laboratory, PO Box 2008, Bethel Valley Road, Oak Ridge, TN 37831-6445, USA.
Sundberg
John P
JP
Awgulewitsch
Alexander
A
Chao
Hanna H J
HH
Carpenter
Donald A
DA
Zhang
Wei-Dong
WD
Rinchik
Eugene M
EM
You
Yun
Y
D000818:Animals; D007446:Chromosome Inversion / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004423:Ear / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006197:Hair / Q000254:growth & development* / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation
D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse