Phenotypic Mutation 'masquerade' (pdf version)
Allelemasquerade
Mutation Type intron
Chromosome15
Coordinate78,352,200 bp (GRCm39)
Base Change C ⇒ T (forward strand)
Gene Tmprss6
Gene Name transmembrane serine protease 6
Synonym(s) matriptase-2, 1300008A22Rik
Chromosomal Location 78,323,867-78,352,834 bp (-) (GRCm39)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygosity for an inactivating mutation of this gene results in hair loss over the entire body except the face, microcytic anemia and female infertility, all reversible by dietary iron supplementation. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_027902; MGI: 1919003

MappedYes 
Amino Acid Change
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold Q9DBI0
SMART Domains Protein: ENSMUSP00000017086
Gene: ENSMUSG00000016942

DomainStartEndE-ValueType
low complexity region 19 39 N/A INTRINSIC
transmembrane domain 57 79 N/A INTRINSIC
Pfam:SEA 88 191 3.2e-13 PFAM
CUB 341 452 3.82e-2 SMART
LDLa 457 489 1.33e-2 SMART
LDLa 490 527 2.31e-9 SMART
LDLa 530 568 1.07e-4 SMART
Tryp_SPc 576 806 3.75e-97 SMART
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Predicted Effect probably benign
Meta Mutation Damage Score Not available question?
Is this an essential gene? Probably nonessential (E-score: 0.067) question?
Phenotypic Category Autosomal Recessive
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance 100% 
Alleles Listed at MGI

All alleles(8) : Targeted, knock-out(2) Targeted, other(2) Gene trapped(1) Chemically induced(3)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01066:Tmprss6 APN 15 78326634 missense probably null 1.00
IGL02474:Tmprss6 APN 15 78326536 missense probably damaging 0.99
cubone UTSW 15 78330857 splice site probably null
dilutional UTSW 15 78328328 missense probably damaging 1.00
Ekans UTSW 15 78343627 splice site probably null
mask UTSW 15 78464455 intron probably benign
zorro UTSW 15 78464552 intron probably benign
BB003:Tmprss6 UTSW 15 78337050 missense probably benign 0.28
BB013:Tmprss6 UTSW 15 78337050 missense probably benign 0.28
PIT1430001:Tmprss6 UTSW 15 78324827 missense probably damaging 1.00
R0285:Tmprss6 UTSW 15 78337068 missense probably damaging 0.99
R1857:Tmprss6 UTSW 15 78336752 missense probably damaging 1.00
R2432:Tmprss6 UTSW 15 78349304 splice site probably benign
R4192:Tmprss6 UTSW 15 78330857 splice site probably null
R4226:Tmprss6 UTSW 15 78330899 missense probably damaging 1.00
R4227:Tmprss6 UTSW 15 78330899 missense probably damaging 1.00
R4334:Tmprss6 UTSW 15 78343627 splice site probably null
R4344:Tmprss6 UTSW 15 78343627 splice site probably null
R4446:Tmprss6 UTSW 15 78337039 missense probably damaging 1.00
R4508:Tmprss6 UTSW 15 78343978 missense probably damaging 1.00
R4643:Tmprss6 UTSW 15 78329556 missense probably damaging 0.98
R4743:Tmprss6 UTSW 15 78327910 missense probably damaging 0.99
R4836:Tmprss6 UTSW 15 78329588 missense probably damaging 1.00
R4859:Tmprss6 UTSW 15 78330877 missense probably damaging 0.99
R4869:Tmprss6 UTSW 15 78327880 splice site probably null
R5197:Tmprss6 UTSW 15 78338389 missense probably damaging 1.00
R5212:Tmprss6 UTSW 15 78330460 missense probably damaging 0.99
R5225:Tmprss6 UTSW 15 78336707 missense probably damaging 0.97
R5569:Tmprss6 UTSW 15 78324503 missense probably damaging 1.00
R5572:Tmprss6 UTSW 15 78326622 missense probably damaging 1.00
R5669:Tmprss6 UTSW 15 78339156 missense possibly damaging 0.86
R5947:Tmprss6 UTSW 15 78336722 missense probably damaging 1.00
R6800:Tmprss6 UTSW 15 78324457 missense probably damaging 1.00
R6941:Tmprss6 UTSW 15 78330977 missense probably damaging 1.00
R6965:Tmprss6 UTSW 15 78328328 missense probably damaging 1.00
R7334:Tmprss6 UTSW 15 78328017 missense unknown
R7338:Tmprss6 UTSW 15 78344019 missense probably damaging 1.00
R7622:Tmprss6 UTSW 15 78330926 missense probably benign 0.40
R7926:Tmprss6 UTSW 15 78337050 missense probably benign 0.28
R7992:Tmprss6 UTSW 15 78326664 missense probably benign 0.11
R8177:Tmprss6 UTSW 15 78349327 missense probably benign 0.01
R8792:Tmprss6 UTSW 15 78328328 missense probably damaging 1.00
R8881:Tmprss6 UTSW 15 78327987 makesense probably null
R9084:Tmprss6 UTSW 15 78338417 missense probably damaging 0.98
R9384:Tmprss6 UTSW 15 78328302 missense probably damaging 0.99
X0025:Tmprss6 UTSW 15 78339295 missense possibly damaging 0.55
Mode of Inheritance Autosomal Recessive
Local Stock Tail Fibroblasts
Repository

none 

Last Updated 2016-05-13 3:09 PM by Peter Jurek
Record Created unknown
Record Posted 2009-02-02
Phenotypic Description

The masquerade mutant phenotype emerged as a visible variant among G3 mice homozygous for mutations induced by ENU.  Mice are balding except for the head (Figure 1).  The balding phenotype highly resembles the phenotypes seen in mask and zorro mice, which carry mutations in Tmprss6.  Masquerade mice also display low serum iron concentrations and reduced female fertility when maintained on a standard laboratory diet.

Nature of Mutation
Because of the phenotypic similarity between masquerade and mutations in Tmprss6,  direct sequencing of Tmprss6 was performed.  A G to A transition at position 2557 of the Tmprss6 transcript was identified, in exon 18 of 18 total exons.
 
2541 GCAGGGTTGGTTAGCTGGGGCCTGGGCTGTGGC
778  -A--G--L--V--S--W--G--L--G--C--G-…
                         deleted
 
Figure 2. Domain structure of TMPRSS6. The C terminus of the protein, including the serine protease domain, is extracellular. Predicted N-glycosylation  sites are noted in violet circles. The masquerade mutation causes a premature stop codon at amino acid 783 (red asterisk) of the TMPRSS6 protein, resulting in deletion of 29 amino acids from the C terminus of the protein. This image is interactive. Click on the image to view other mutations found in TMPRSS6 (red). Click on the mutations for more specific information. 
The mutated nucleotide is indicated in red lettering, and creates a premature stop codon in place of tryptophan 783 resulting in deletion of 29 amino acids from the C terminus of the protein (Figure 2). The mutation truncates the protein near the end of the C-terminal serine protease domain (residues 576-806).  As the catalytic residues (S762, D668 and H617) necessary for protease activity are unaffected, it is unknown if the truncated protein retains any function.  It is possible that the mutation may destabilize the protein and cause its degradation.
 
Please see the record for mask for information about Tmprss6.
Illustration of Mutations in
Gene & Protein
Primers Primers cannot be located by automatic search.
Genotyping
Masquerade genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide change.
 
Primers for PCR amplification
Masq (F): 5’- GCAAGAAAGATGCCTGCCAGGTAAC  -3’
Masq (R): 5’- GGCATAAGGTGCATGAAGCCACTC -3’
 
PCR program (use SIGMA JumpStart REDTaq)
1) 94°C             2:00
2) 94°C             0:30
3) 56°C             0:30
4) 72°C             1:00
5) repeat steps (2-4) 29X
6) 72°C             7:00
7) 4°C               ∞
 
Primers for sequencing
Masq_seq (F): 5’- CCTGCCAGGTAACTAGCTATG  -3’
Masq_seq (R1): 5'- TGTAGAACAGCCCTCAGGTC -3'
Masq_seq (R2): 5’- TTAGCAGGGTCACTTGCC -3’
 
The following sequence of 990 nucleotides (from Genbank genomic region NC_000081 for linear genomic sequence of Tmprss6) is amplified:
 
 
28008                                                    gca agaaagatgc
28021 ctgccaggta actagctatg gggtgtgtcc tgaagtgggg gggatgacga ctgctcccac
28081 tttacagatg gggagcctga ggtcttcaga ggctgagggg cctgctcatg gctgcaatgg
28141 cacatggcag accccttggg gcggaaggtc tttcgctctg ctccttccta tcctaagacc
28201 ttggggctgg agtcacacgg gtagaccctc accctgaggc agtcgcatct ctcctgtttt
28261 agggtgactc tggaggccca ctggtttgca gggagcccag tggccgctgg ttcctggcag
28321 ggttggttag ctggggcctg ggctgtggcc gacccaattt ctttggcgtc tacacccgtg
28381 tcacacgtgt gatcaactgg atccagcagg tgctgacctg agggctgttc tacagagctg
28441 gacctgcctc caggccaagt tcagggtgtc cacccagcca ggacacaagt attctggggc
28501 aagtgaccct gctaaggcct gtttccctca ggcctacccc agtgacagta cagagaagga
28561 tgtcagctgg tggttaggat gcctcctgag gtccaggggc cagcctcggc taggtttcac
28621 ttctaaccct ttcttattct agtcctttcc cctccctgct cctaccactg ttttggagtg
28681 gggtctggcg gccatgacct tggcctccgg gtctctgtag gaaagaaaga atccttcccc
28741 ttgcaaaagc ctcttggggg aactgcacag agaaagaagg tgcctctatc aaggctctat
28801 cagagccctt gagtctgcca agtgggctgt actctaagcc aaatcaccgg gcagcctcag
28861 ctgcagatgc ctgctgaagc tctgcctgct acaggggcct ccctgccatt cactggaggc
28921 ccactgtctg ttctgggaat aaagcacttg accaagccct gacactgata tctgagtggc
28981 ttcatgcacc ttatgcc
PCR primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated G is shown in red text.
Science Writers Nora G. Smart
Illustrators Diantha La Vine
AuthorsAmanda Blasius, Xin Du, Bruce Beutler
Edit History
2011-01-07 9:20 AM (current)
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