Phenotypic Mutation 'sariba' (pdf version)
Allelesariba
Mutation Type missense
Chromosome15
Coordinate66,566,719 bp (GRCm39)
Base Change A ⇒ G (forward strand)
Gene Tg
Gene Name thyroglobulin
Synonym(s) Tgn
Chromosomal Location 66,542,606-66,722,570 bp (+) (GRCm39)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]
PHENOTYPE: Mice homozygous for a spontaneous mutation exhibit enlarged thyroid gland, hypothyroidism, abnormal thyroid gland morphology, and decreased body weight. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_027902; MGI:1919003

MappedYes 
Amino Acid Change Serine changed to Glycine
Institutional SourceBeutler Lab
Gene Model predicted gene model for protein(s): [ENSMUSP00000070239]
AlphaFold no structure available at present
SMART Domains Protein: ENSMUSP00000070239
Gene: ENSMUSG00000053469
AA Change: S1256G

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
TY 50 97 5.9e-16 SMART
TY 118 165 5.59e-17 SMART
Pfam:Thyroglobulin_1 174 252 4e-9 PFAM
TY 317 363 4.36e-19 SMART
low complexity region 495 504 N/A INTRINSIC
TY 617 662 3.58e-15 SMART
TY 684 730 1.47e-16 SMART
TY 880 926 1.51e-4 SMART
TY 1029 1078 1.21e-12 SMART
TY 1106 1150 7.56e-5 SMART
TY 1167 1215 7.26e-16 SMART
low complexity region 1244 1255 N/A INTRINSIC
Pfam:GCC2_GCC3 1464 1509 2.7e-16 PFAM
TY 1519 1568 9.81e-13 SMART
Pfam:COesterase 2181 2717 8.4e-140 PFAM
Predicted Effect probably benign

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)
(Using ENSMUST00000065916)
Meta Mutation Damage Score 0.0941 question?
Is this an essential gene? Probably nonessential (E-score: 0.096) question?
Phenotypic Category Unknown
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance  
Alleles Listed at MGI

All Mutations and Alleles(14) : Chemically induced (ENU)(4) Chemically induced (other)(3) Endonuclease-mediated(1) Gene trapped(1) Radiation induced(2) Spontaneous(1) Targeted(1) Transgenic(1)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00157:Tg APN 15 66719015 missense probably damaging 1.00
IGL00230:Tg APN 15 66699139 missense probably benign 0.00
IGL00324:Tg APN 15 66565273 missense probably benign
IGL00428:Tg APN 15 66645273 missense probably benign 0.33
IGL00703:Tg APN 15 66568338 missense probably benign 0.34
IGL00808:Tg APN 15 66555662 missense probably damaging 1.00
IGL00833:Tg APN 15 66560650 missense probably benign 0.34
IGL00899:Tg APN 15 66545922 critical splice donor site probably null
IGL00921:Tg APN 15 66636302 missense probably benign 0.28
IGL00975:Tg APN 15 66553731 missense probably benign
IGL01288:Tg APN 15 66608125 missense possibly damaging 0.81
IGL01397:Tg APN 15 66567941 splice site probably benign
IGL01634:Tg APN 15 66601415 missense probably benign 0.34
IGL01646:Tg APN 15 66549936 missense probably damaging 1.00
IGL01704:Tg APN 15 66543200 missense probably damaging 0.98
IGL01958:Tg APN 15 66631335 missense probably benign 0.06
IGL02093:Tg APN 15 66564223 missense possibly damaging 0.83
IGL02113:Tg APN 15 66577179 missense probably benign 0.08
IGL02138:Tg APN 15 66589082 missense probably benign 0.01
IGL02156:Tg APN 15 66577197 missense probably benign 0.19
IGL02169:Tg APN 15 66629792 missense probably benign 0.04
IGL02342:Tg APN 15 66636140 missense probably benign
IGL02434:Tg APN 15 66636191 missense probably damaging 0.97
IGL02506:Tg APN 15 66613443 missense possibly damaging 0.71
IGL02513:Tg APN 15 66577123 missense probably benign
IGL02549:Tg APN 15 66711210 missense probably damaging 1.00
IGL02669:Tg APN 15 66620575 splice site probably benign
IGL02756:Tg APN 15 66606435 missense probably benign
IGL02800:Tg APN 15 66629735 missense probably damaging 1.00
IGL02828:Tg APN 15 66554243 missense probably damaging 1.00
IGL02927:Tg APN 15 66549942 missense probably damaging 1.00
IGL03061:Tg APN 15 66543254 missense probably damaging 1.00
IGL03105:Tg APN 15 66586955 missense probably benign 0.01
IGL03160:Tg APN 15 66711152 nonsense probably null
IGL03242:Tg APN 15 66555647 missense probably damaging 0.99
Also_ran UTSW 15 66550688 missense probably damaging 1.00
bedraggled UTSW 15 66612563 missense probably damaging 1.00
foster UTSW 15 66565109 nonsense probably null
hognose UTSW 15 66589057 missense probably damaging 0.99
ito UTSW 15 66638011 nonsense probably null
ito2 UTSW 15 66543245 missense probably damaging 1.00
ito3 UTSW 15 66645323 missense probably damaging 1.00
ito4 UTSW 15 66568369 missense possibly damaging 0.47
Papua UTSW 15 66545899 missense probably damaging 1.00
Pipistrella UTSW 15 66567984 missense probably damaging 1.00
pluribus UTSW 15 66587012 missense probably damaging 0.98
samarai UTSW 15 66629855 critical splice donor site probably null
ticker UTSW 15 66699231 nonsense probably null
Vampire UTSW 15 66554676 missense probably damaging 1.00
IGL03134:Tg UTSW 15 66612567 missense probably damaging 1.00
P0019:Tg UTSW 15 66560712 missense probably benign 0.01
R0121:Tg UTSW 15 66612630 missense probably benign 0.04
R0135:Tg UTSW 15 66566719 missense probably benign 0.01
R0227:Tg UTSW 15 66570295 missense possibly damaging 0.84
R0448:Tg UTSW 15 66636291 missense probably damaging 1.00
R0453:Tg UTSW 15 66700382 missense probably benign 0.09
R0504:Tg UTSW 15 66554253 missense probably damaging 0.97
R0543:Tg UTSW 15 66601446 missense probably benign 0.13
R0638:Tg UTSW 15 66589057 missense probably damaging 0.99
R0639:Tg UTSW 15 66613333 critical splice acceptor site probably null
R0646:Tg UTSW 15 66601475 missense probably damaging 0.99
R0666:Tg UTSW 15 66609370 missense probably benign
R0673:Tg UTSW 15 66613333 critical splice acceptor site probably null
R0689:Tg UTSW 15 66711253 splice site probably benign
R0704:Tg UTSW 15 66629729 missense probably benign 0.02
R0730:Tg UTSW 15 66550638 missense probably damaging 1.00
R0830:Tg UTSW 15 66596993 missense probably damaging 1.00
R0959:Tg UTSW 15 66579859 missense probably damaging 0.98
R1027:Tg UTSW 15 66544258 missense possibly damaging 0.65
R1061:Tg UTSW 15 66570408 missense probably benign 0.09
R1086:Tg UTSW 15 66555911 missense probably benign
R1103:Tg UTSW 15 66591504 missense probably benign 0.45
R1240:Tg UTSW 15 66700397 missense probably benign 0.16
R1281:Tg UTSW 15 66568338 missense probably benign 0.34
R1470:Tg UTSW 15 66721312 missense possibly damaging 0.95
R1470:Tg UTSW 15 66721312 missense possibly damaging 0.95
R1531:Tg UTSW 15 66722351 missense probably benign 0.02
R1544:Tg UTSW 15 66577081 missense probably benign 0.04
R1550:Tg UTSW 15 66565279 missense possibly damaging 0.52
R1575:Tg UTSW 15 66601534 critical splice donor site probably null
R1638:Tg UTSW 15 66568015 nonsense probably null
R1655:Tg UTSW 15 66700417 critical splice donor site probably null
R1671:Tg UTSW 15 66564236 missense possibly damaging 0.89
R1789:Tg UTSW 15 66609397 missense probably benign 0.00
R1883:Tg UTSW 15 66543158 missense probably damaging 1.00
R1984:Tg UTSW 15 66554691 missense probably benign
R2063:Tg UTSW 15 66700402 missense probably damaging 1.00
R2092:Tg UTSW 15 66721456 missense probably null 0.26
R2109:Tg UTSW 15 66601443 missense probably benign 0.02
R2128:Tg UTSW 15 66566743 missense probably benign 0.10
R2129:Tg UTSW 15 66566743 missense probably benign 0.10
R2207:Tg UTSW 15 66553788 missense probably benign 0.15
R2219:Tg UTSW 15 66553782 missense probably benign 0.03
R2228:Tg UTSW 15 66545860 missense probably damaging 0.99
R2229:Tg UTSW 15 66545860 missense probably damaging 0.99
R2259:Tg UTSW 15 66555747 missense probably benign
R2994:Tg UTSW 15 66553802 missense probably benign
R3904:Tg UTSW 15 66638011 nonsense probably null
R3946:Tg UTSW 15 66545872 missense probably damaging 1.00
R3965:Tg UTSW 15 66556039 missense probably benign
R4245:Tg UTSW 15 66568318 missense possibly damaging 0.68
R4451:Tg UTSW 15 66637996 missense probably benign 0.01
R4487:Tg UTSW 15 66543245 missense probably damaging 1.00
R4489:Tg UTSW 15 66579791 missense probably damaging 1.00
R4623:Tg UTSW 15 66607120 missense probably benign 0.23
R4659:Tg UTSW 15 66545769 missense possibly damaging 0.67
R4728:Tg UTSW 15 66554676 missense probably damaging 1.00
R4760:Tg UTSW 15 66565168 missense probably damaging 1.00
R4797:Tg UTSW 15 66629855 critical splice donor site probably null
R4944:Tg UTSW 15 66636186 missense probably damaging 1.00
R4998:Tg UTSW 15 66545899 missense probably damaging 1.00
R5009:Tg UTSW 15 66568435 missense probably benign 0.01
R5025:Tg UTSW 15 66579779 missense probably damaging 1.00
R5035:Tg UTSW 15 66553662 splice site probably null
R5049:Tg UTSW 15 66699231 nonsense probably null
R5073:Tg UTSW 15 66607101 missense probably benign 0.05
R5169:Tg UTSW 15 66550629 nonsense probably null
R5185:Tg UTSW 15 66645323 missense probably damaging 1.00
R5227:Tg UTSW 15 66631416 missense possibly damaging 0.87
R5300:Tg UTSW 15 66550704 missense probably damaging 1.00
R5334:Tg UTSW 15 66549904 missense probably damaging 1.00
R5339:Tg UTSW 15 66549942 missense probably damaging 1.00
R5402:Tg UTSW 15 66611017 missense probably damaging 0.98
R5441:Tg UTSW 15 66568369 missense possibly damaging 0.47
R5509:Tg UTSW 15 66699142 missense probably benign 0.45
R5580:Tg UTSW 15 66557149 missense possibly damaging 0.66
R5582:Tg UTSW 15 66565284 missense probably damaging 1.00
R5624:Tg UTSW 15 66709906 missense probably benign 0.11
R5686:Tg UTSW 15 66560738 missense probably benign 0.28
R6042:Tg UTSW 15 66555842 missense probably benign 0.01
R6122:Tg UTSW 15 66700306 missense probably damaging 1.00
R6146:Tg UTSW 15 66545216 splice site probably null
R6159:Tg UTSW 15 66607096 missense possibly damaging 0.71
R6223:Tg UTSW 15 66579771 missense probably benign 0.15
R6480:Tg UTSW 15 66543160 missense probably damaging 1.00
R6505:Tg UTSW 15 66631407 missense probably damaging 0.99
R6531:Tg UTSW 15 66711211 missense probably damaging 0.99
R6614:Tg UTSW 15 66607108 missense probably damaging 0.99
R6698:Tg UTSW 15 66711211 missense probably damaging 1.00
R6798:Tg UTSW 15 66550688 missense probably damaging 1.00
R6837:Tg UTSW 15 66567984 missense probably damaging 1.00
R6861:Tg UTSW 15 66560740 missense probably benign 0.00
R6888:Tg UTSW 15 66568095 missense probably damaging 0.99
R6933:Tg UTSW 15 66636158 missense possibly damaging 0.73
R6983:Tg UTSW 15 66565207 missense probably benign 0.01
R7078:Tg UTSW 15 66545392 missense probably damaging 1.00
R7244:Tg UTSW 15 66612563 missense probably damaging 1.00
R7320:Tg UTSW 15 66566633 missense possibly damaging 0.71
R7334:Tg UTSW 15 66597121 missense probably benign 0.01
R7418:Tg UTSW 15 66568432 missense probably damaging 0.99
R7485:Tg UTSW 15 66568437 missense probably benign 0.04
R7524:Tg UTSW 15 66568010 missense probably benign 0.01
R7529:Tg UTSW 15 66566617 missense probably damaging 0.99
R7540:Tg UTSW 15 66561776 missense probably benign 0.16
R7583:Tg UTSW 15 66636267 missense probably damaging 1.00
R7594:Tg UTSW 15 66601432 missense probably benign 0.20
R7667:Tg UTSW 15 66587012 missense probably damaging 0.98
R7722:Tg UTSW 15 66636158 missense possibly damaging 0.73
R7790:Tg UTSW 15 66721453 missense probably damaging 0.99
R7838:Tg UTSW 15 66565112 missense probably benign 0.00
R7890:Tg UTSW 15 66555663 missense probably damaging 1.00
R7904:Tg UTSW 15 66577128 missense probably benign 0.08
R7919:Tg UTSW 15 66555923 missense possibly damaging 0.73
R7921:Tg UTSW 15 66555642 missense probably benign 0.08
R8037:Tg UTSW 15 66560724 missense probably benign 0.00
R8038:Tg UTSW 15 66560724 missense probably benign 0.00
R8214:Tg UTSW 15 66645247 missense probably damaging 1.00
R8304:Tg UTSW 15 66565109 nonsense probably null
R8688:Tg UTSW 15 66566802 critical splice donor site probably benign
R8709:Tg UTSW 15 66553786 missense probably benign 0.08
R8714:Tg UTSW 15 66555891 missense probably damaging 0.97
R8901:Tg UTSW 15 66557184 missense probably damaging 1.00
R8917:Tg UTSW 15 66645332 critical splice donor site probably null
R9023:Tg UTSW 15 66555522 missense probably damaging 1.00
R9232:Tg UTSW 15 66570310 missense probably benign 0.01
R9310:Tg UTSW 15 66699118 missense possibly damaging 0.69
R9361:Tg UTSW 15 66557246 missense possibly damaging 0.50
R9389:Tg UTSW 15 66561173 missense probably benign 0.04
R9501:Tg UTSW 15 66718923 missense possibly damaging 0.52
R9510:Tg UTSW 15 66545913 missense probably damaging 1.00
R9594:Tg UTSW 15 66607109 nonsense probably null
R9629:Tg UTSW 15 66555587 missense possibly damaging 0.95
R9701:Tg UTSW 15 66637991 missense probably benign 0.03
R9743:Tg UTSW 15 66561839 missense probably benign 0.18
R9748:Tg UTSW 15 66719008 missense possibly damaging 0.91
T0975:Tg UTSW 15 66560712 missense probably benign 0.01
X0005:Tg UTSW 15 66560712 missense probably benign 0.01
X0065:Tg UTSW 15 66554303 missense probably damaging 1.00
X0067:Tg UTSW 15 66620592 missense probably benign 0.10
Z1177:Tg UTSW 15 66721396 missense probably benign 0.02
Z1177:Tg UTSW 15 66557159 missense possibly damaging 0.49
Mode of Inheritance Unknown
Local Stock
Repository
Last Updated 2019-09-04 9:30 PM by Anne Murray
Record Created 2019-01-23 10:17 AM by Bruce Beutler
Record Posted 2019-02-01
Phenotypic Description

Figure 1. Sariba mice exhibit increased frequencies of peripheral CD44+ T cells. Flow cytometric analysis of peripheral blood was utilized to determine T cell frequency. Raw data are shown. Abbreviations: WT, wild-type; REF, homozygous reference mice; HET, heterozygous variant mice; VAR, homozygous variant mice. Mean (μ) and standard deviation (σ) are indicated.

The sariba phenotype was identified among G3 mice of the pedigree R0135, some of which showed increased frequencies of CD44+ T cells in the peripheral blood (Figure 1).

Nature of Mutation

Figure 2. Linkage mapping of the increased CD44+ T cell frequency using a recessive model of inheritance. Manhattan plot shows -log10 P values (Y-axis) plotted against the chromosome positions of 79 mutations (X-axis) identified in the G1 male of pedigree R0135. Raw phenotype data are shown for single locus linkage analysis without consideration of G2 dam identity. Horizontal pink and red lines represent thresholds of P = 0.05, and the threshold for P = 0.05 after applying Bonferroni correction, respectively.

Whole exome HiSeq sequencing of the G1 grandsire identified 79 mutations. The CD44+ T cell phenotype was linked to mutations in three genes on chromosome 15: Tg, Mei1, and Pnpla5. The mutation in Tg was presumed causative as the immune phenotype mimicked that of other mutant Tg alleles. The mutation in Tg is an A to G transition at base pair 66,694,870 (v38) on chromosome 15, or base pair 24,117 in the GenBank genomic region NC_000081 encoding Tg. Linkage was found with a recessive model of inheritance, wherein three variant homozygotes departed phenotypically from three homozygous reference mice and five heterozygous mice with a P value of 0.000489 (Figure 2).

The mutation corresponds to residue 3,788 in the NM_009375 mRNA sequence in exon 5 of 48 total exons. 


 

3773 CGCCAGGGCCTCCGGAGTGCGTTTTCACCAGGG

1251 -R--Q--G--L--R--S--A--F--S--P--G-

The mutated nucleotide is indicated in red. The mutation results in a serine to glycine substitution of position 1,256 (S1256G) in the thyroglobulin protein, and is strongly predicted by PolyPhen-2 to be benign (score = 0.010).

Illustration of Mutations in
Gene & Protein
Protein Prediction

Figure 3. The protein domains of TG. The TG protein has a signal peptide (amino acids 1-20), 11 type 1, three type 2, three type 3a, and two type 3b Cys-rich repeats followed by an acetylcholinesterase (AChE)-like domain. Tg can be divided into distinct regions: region I containing 10 type 1 repeats along with linker and hinge segments; region II-III contains the type 2 repeats, the type 1 repeat, and the type 3 repeats; and the AchE-like domain. The location of the sariba mutation is indicated. Other mutations found in TG are noted in red. This image is interactive. Click on the mutations for more specific information.

Tg encodes thyroglobulin (Tg), a precursor of two thyroid hormones: 3,5,3’ triiodothyronine (T3) and 3,5,3’,5’ tetraiodothyronine (thyroxine; T4). Tg has a 20-amino acid signal peptide (amino acids 1-20). The remaining Tg protein is comprised of 11 type 1, three type 2, three type 3a, and two type 3b Cys-rich repeats followed by an acetylcholinesterase (AChE)-like domain (Figure 3(1-3). Tg can be divided into distinct regions: region I contains the ten type I repeats between amino acids 32 and 1211 along with linker and hinge segments; region II-III contains the type 2 repeats, the type I repeat at amino acids 1510-1564, and the type 3 repeats; and the AchE-like domain (amino acids 2181-2717) (4). Within the secretory system, Tg undergoes several posttranslational modifications including glycosylation, sialylation, sulfation, phosphorylation, iodination, and formation of approximately 60 intrachain disulfide binds per monomer. Upon reaching the follicular lumen, several tyrosines are iodinated. Several of the iodinated tyrosines are coupled to form T3and T4. The release of thyroid hormone occurs after several steps including intra-and extracellular proteolytic degradation of Tg by several proteases.

The sariba mutation results in a serine to glycine substitution of position 1,256 (S1256G) within an undefined region between the tenth type 1 Cys-rich repeat and the first type 2 Cys-rich repeat.

For more information about Tg, please see the record for ito.

Putative Mechanism

Within the thyroid gland, epithelial cells synthesize thyroid hormones and are arranged as thyroid follicles. Between the thyroid follicles are parafollicular (alternatively, C cells), which secrete the hormone calcitonin. Tg is secreted by the thyroid cell into the follicular lumen by regulated (nonconstitutive), merocrine secretion. Upon stimulation by thyroid-stimulating hormone (TSH), Tg is reabsorbed by endocytosis/pinocytosis or phagocytosis (rodents only) to form endocytic/pinocytic vesicles or phagosomes, respectively. After release into the blood stream, T3 and T4 control metabolism. Mutations in TG have been linked to congenital goiter with hypothyroidism (euthyroidism) (OMIM: #274700(5-7) as well as endemic and euthyroid nonendemic simple goiter (8-10). The 8q24 locus, which contains TG, is linked to autoimmune thyroid disease (AITD) including Graves’ disease and Hashimoto’s thyroiditis. Sequence analysis determined that TG is a AITD susceptibility gene in both humans and mice (11) (OMIM: #608175).

The cog/cog (Tgcog; MGI:1856829) mouse model has a point mutation in Tg that causes a Leu to Pro substitution at amino acid 2263 (12;13). The cog/cog mouse exhibits congenital hypothyroidism with goiter as well as abnormal growth, mild anemia, and defects in central nervous system development (e.g., microcephalic cerebrum with hypomyelination) (14;15).  Tg expression is normal in the cog/cog mice, but the Tg protein exhibits increased proteolysis (16;17). Furthermore, the Tgcog/cog protein exhibited abnormal folding, dimerication, and export as well increased levels of several ER molecular chaperones, all of which are indicative of an ER storage defect (18). As a result, the levels of total serum T4 and T3 are low with a concomitant increase in serum TSH levels (15). A second mouse model has an ENU-induced mutation in Tg (TgR1471X; MGI:5694939). The TgR1471X mice exhibited stunted growth (19). The sariba phenotype indicates that Tg function is impaired. Expression and localization of Tgsariba has not been examined.

Primers PCR Primer
sariba_pcr_F: CTGCCTGTCTGGTGAAACTGAGAG
sariba_pcr_R: ACCTGACGTGAAAAGGCTGTACTTG

Sequencing Primer
sariba_seq_F: CTGAGAGACAGTGGACTTATCC
sariba_seq_R: CTTGAGTGGCAGGAAGTCTCTAAC
Genotyping

PCR program

1) 94°C 2:00
2) 94°C 0:30
3) 55°C 0:30
4) 72°C 1:00
5) repeat steps (2-4) 40x
6) 72°C 10:00
7) 4°C hold


The following sequence of 495 nucleotides is amplified (chromosome 15, + strand):


1   ctgcctgtct ggtgaaactg agagacagtg gacttatcca gtgaggagtc atagaaggag
61  ggaaaagaac taggccctga cagagcagga cacaatgaga aagggcttgg ggaacaatca
121 agggaagcag atgggtaggc agagctgggt ttaagtctgg gaggtaccca tgcctcttct
181 ccatcgctgc tcctaggccc acagtgtcca ctgccattct ctgggtcaga tgtggctgat
241 ggagtgatct tctgcgagac agcctctagc tcaggagtga cgactgttca gcagtgccag
301 ctgctgtgcc gccagggcct ccggagtgcg ttttcaccag ggccactgat ttgtagcctg
361 gagagtcagc actgggtgac actgccacca ccccgagcct gtcaaagtga gtagcactgg
421 ggagactcat ccttcactct cagggctatt gttagagact tcctgccact caagtacagc
481 cttttcacgt caggt


Primer binding sites are underlined and the sequencing primers are highlighted; the mutated nucleotide is shown in red.

References
Science Writers Anne Murray
Illustrators Diantha La Vine
AuthorsJin Huk Choi, Xue Zhong, and Bruce Beutler