Phenotypic Mutation 'zorro' (pdf version)
Allelezorro
Mutation Type intron
Chromosome15
Coordinate78,464,552 bp (GRCm38)
Base Change G ⇒ A (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
masquerade UTSW 15 78352200 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 Sperm, gDNA
MMRRC Submission 030754-UCD
Last Updated 2016-05-13 3:09 PM by Peter Jurek
Record Created unknown
Record Posted 2008-09-25
Phenotypic Description
The zorro mutant phenotype emerged as a visible variant among G3 mice homozygous for mutations induced by ENU.  The index zorro mutant initially grew a normal, full coat of hair, but then gradually lost hair from the trunk until it was almost nude by approximately six weeks of age.  Facial hair was preserved in the zorro mouse.  The visible phenotype of zorro appeared identical to the mask phenotype.
 
Like mask mutants, zorro mice have low serum iron concentration when maintained on a standard laboratory diet.
Nature of Mutation
Because of the phenotypic similarity between zorro and mask, direct sequencing of Tmprss6 was performed. A C to T transition at position 2004 of the Tmprss6 transcript was identified, in exon 15 of 18 total exons.
 
1989 CTCCAGATTCGGGGTCGACACATCTGTGGGGGG
594  -L--Q--I--R--G--R--H--I--C--G--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 zorro mutation causes a premature stop codon at amino acid 599 (red asterisk) of the TMPRSS6 protein, resulting in deletion of 212 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 arginine 599 resulting in deletion of 212 amino acids from the C terminus of the protein (Figure 2). The mutation truncates the protein within the serine protease domain (residues 576-806), also deleting all three residues of the catalytic triad (S762, D668 and H617). At minimum, the mutant protein is expected to be completely deficient in protease activity; 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

Zorro genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transition.

 

Primers

zorro (F): 5’- TGTGTGAAGAAGCCCAACCCAGAG -3’

zorro (R): 5’- CAGTACAGCCATTGGCATGTAGGAG -3’

 

PCR program

1) 95°C             2:00

2) 95°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

zorro_seq(F): 5’- TCAGATTGCAGAGACGGCTC -3’

zorro_seq(R): 5’- CTAGCAACACACTGCATGTTTG -3’

 

The following sequence of 769 nucleotides (from Genbank genomic region NC_000081 for linear genomic sequence of Tmprss6) is amplified:

24467                                                   tgtg tgaagaagcc

24481 caacccagag tgtgacggcc agtcagattg cagagacggc tcagatgagc aacactgtgg

24541 tgagcctgtt agccagggct gtgcatgaag gccaggcctg ggagtggggc atggactctc

24601 atgggaagca ggaggggagt gtcaccatgt gtctgttccg tgcctagctg tctctgtcac

24661 ctgttcctgg gcctagctct cctttccccc cacacctctt cattgcttta ctttgttgtc

24721 tgtctccatt tctcacgagc ctttcttcct cccctctcct tcttctctgt ccccccccac

24781 cattatcaga ctgtggcctc cagggcctct ccagccgtat tgtgggcggg accgtgtcct

24841 ccgagggtga gtggccatgg caggccagcc tccagattcg gggtcgacac atctgtgggg

24901 gggctctcat cgctgaccgc tgggtcataa cggccgccca ctgcttccag gaggacaggt

24961 gaggggacac cacagggcct ggggatgggc atagggaagg accgtgggag atacagcatg

25021 cacaaactgt actcagacag aggaaagggt agagagcacc tggaggggct gccatgtggg

25081 atctggtctg gttctgttgc aaacatgcag tgtgttgcta ggctggctgt tcagcctttc

25141 tgtgttcccc tcttgcttta agatgagacc actatcattt attcattcca tttacccaat

25201 gactgcactc ctcctacatg ccaatggctg tactg

Primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated C is indicated in red.

Science Writers Eva Marie Y. Moresco
Illustrators Diantha La Vine
AuthorsXin Du, Bruce Beutler
Edit History
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