Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota.
Suppressor of tumorigenicity 14 (St14) encodes matriptase, a serine protease, which regulates processing of profilaggrin to filaggin in vivo. Here, we report that transgenic mice with 1% of wild-type St14 levels (St14(hypo/-)) display aberrant processing of profilaggrin and model human ichthyotic skin phenotypes. Scaling of the skin appears at 1 week of age with underlying epidermal acanthosis and orthohyperkeratosis as well as a CD4+ T-cell dermal infiltrate. Upregulation of antimicrobial peptides occurs when challenged by exposure to the postnatal environment. Direct genomic sequencing of bacterial 16S rRNA genes to query microbial diversity identifies a significant shift in both phylogeny and community structure between St14(hypo/-) mice and control littermates. St14(hypo/-) mice have a selective shift in resident skin microbiota with a decrease of the dominant genus of skin bacteria, Pseudomonas and an accompanying increase of Corynebacterium and Streptococcus. St14(hypo/-) mice provide early evidence that the cutaneous microbiome can be specifically altered by genetic state, which may play an important role in modulating skin disease.
Scharschmidt
Tiffany C
TC
National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
List
Karin
K
Grice
Elizabeth A
EA
Szabo
Roman
R
Renaud
Gabriel
G
Lee
Chyi-Chia R
CC
Wolfsberg
Tyra G
TG
Bugge
Thomas H
TH
Segre
Julia A
JA
D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D003352:Corynebacterium; D004195:Disease Models, Animal; D000091344:Filaggrin Proteins; D007057:Ichthyosis / Q000378:metabolism / Q000382:microbiology*; D007113:Immunity, Innate; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D011549:Pseudomonas; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000382:microbiology*; D013291:Streptococcus
D023181:Antimicrobial Cationic Peptides; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D012697:Serine Endopeptidases; C485595:matriptase