Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation

Murgiano, Leonardo; Shirokova, Vera; Welle, Monika Maria; Jagannathan, Vidhya; Plattet, Philippe; Oevermann, Anna; Pienkowska-Schelling, Aldona; Gallo, Daniele; Gentile, Arcangelo; Mikkola, Marja; Drögemüller, Cord (2015). Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation. PLoS genetics, 11(7), e1005427. Public Library of Science 10.1371/journal.pgen.1005427

[img]
Preview
Text
doi_10.1371_journal.pgen.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (17MB) | Preview

Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal species, we identified TSR2 as a regulator of hair follicle development.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Murgiano, Leonardo; Welle, Monika Maria; Jagannathan, Vidya; Plattet, Philippe; Oevermann, Anna and Drögemüller, Cord

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1553-7390

Publisher:

Public Library of Science

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

24 Aug 2015 11:19

Last Modified:

12 Dec 2018 11:26

Publisher DOI:

10.1371/journal.pgen.1005427

PubMed ID:

26203908

BORIS DOI:

10.7892/boris.71097

URI:

https://boris.unibe.ch/id/eprint/71097

Actions (login required)

Edit item Edit item
Provide Feedback