Phenotypic Mutation 'paleo' (pdf version)
Allele | paleo |
Mutation Type |
missense
|
Chromosome | 4 |
Coordinate | 101,602,842 bp (GRCm39) |
Base Change | T ⇒ A (forward strand) |
Gene |
Lepr
|
Gene Name | leptin receptor |
Synonym(s) | leptin receptor gene-related protein, obl, Obr, Leprb, obese-like, Modb1, LEPROT, OB-RGRP |
Chromosomal Location |
101,574,601-101,672,549 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 belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010] PHENOTYPE: Homozygous mutants are hyperphagic, low-activity, poorly cold-adapted, sterile and have enhanced fat conversion. They are obese, hyperinsulinemic and, on certain strains, severely hyperglycemic. Heterozygotes are normal but resistant to prolonged fasting. [provided by MGI curators]
|
Accession Number | NCBI RefSeq: NM_146146, NM_010704, NM_001122899; MGI:104993
|
Mapped | Yes |
Amino Acid Change |
Methionine changed to Lysine
|
Institutional Source | Beutler Lab |
Gene Model |
predicted gene model for protein(s):
[ENSMUSP00000037385]
[ENSMUSP00000099838]
[ENSMUSP00000102534]
|
AlphaFold |
P48356 |
SMART Domains |
Protein: ENSMUSP00000037385 Gene: ENSMUSG00000057722 AA Change: M210K
Domain | Start | End | E-Value | Type |
transmembrane domain
|
7 |
29 |
N/A |
INTRINSIC |
FN3
|
236 |
315 |
1.5e-5 |
SMART |
Pfam:Lep_receptor_Ig
|
328 |
418 |
6.3e-23 |
PFAM |
FN3
|
535 |
618 |
4.93e-1 |
SMART |
FN3
|
641 |
721 |
3.25e1 |
SMART |
FN3
|
736 |
818 |
2.35e0 |
SMART |
transmembrane domain
|
838 |
860 |
N/A |
INTRINSIC |
low complexity region
|
908 |
921 |
N/A |
INTRINSIC |
low complexity region
|
1050 |
1065 |
N/A |
INTRINSIC |
|
Predicted Effect |
possibly damaging
PolyPhen 2
Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)
(Using ENSMUST00000037552)
|
SMART Domains |
Protein: ENSMUSP00000099838 Gene: ENSMUSG00000057722 AA Change: M210K
Domain | Start | End | E-Value | Type |
transmembrane domain
|
7 |
29 |
N/A |
INTRINSIC |
FN3
|
236 |
315 |
1.5e-5 |
SMART |
Pfam:Lep_receptor_Ig
|
329 |
420 |
2.6e-29 |
PFAM |
FN3
|
535 |
618 |
4.93e-1 |
SMART |
FN3
|
641 |
721 |
3.25e1 |
SMART |
FN3
|
736 |
818 |
2.35e0 |
SMART |
transmembrane domain
|
838 |
860 |
N/A |
INTRINSIC |
|
Predicted Effect |
possibly damaging
PolyPhen 2
Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)
(Using ENSMUST00000102777)
|
SMART Domains |
Protein: ENSMUSP00000102534 Gene: ENSMUSG00000057722 AA Change: M210K
Domain | Start | End | E-Value | Type |
transmembrane domain
|
7 |
29 |
N/A |
INTRINSIC |
FN3
|
236 |
315 |
1.5e-5 |
SMART |
Pfam:Lep_receptor_Ig
|
329 |
420 |
2.6e-29 |
PFAM |
FN3
|
535 |
618 |
4.93e-1 |
SMART |
FN3
|
641 |
721 |
3.25e1 |
SMART |
FN3
|
736 |
818 |
2.35e0 |
SMART |
transmembrane domain
|
838 |
860 |
N/A |
INTRINSIC |
|
Predicted Effect |
possibly damaging
PolyPhen 2
Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)
(Using ENSMUST00000106921)
|
Meta Mutation Damage Score |
0.9083 |
Is this an essential gene? |
Non Essential (E-score: 0.000) |
Phenotypic Category |
Autosomal Recessive |
Candidate Explorer Status |
loading ... |
Single pedigree Linkage Analysis Data
|
|
Penetrance | |
Alleles Listed at MGI | All mutations/alleles(42) : Chemically induced (ENU)(8) Spontaneous(14) Targeted(19) Transgenic(1)
|
Lab Alleles |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00089:Lepr
|
APN |
4 |
101672232 |
missense |
probably benign |
|
IGL01111:Lepr
|
APN |
4 |
101671852 |
missense |
possibly damaging |
0.77 |
IGL01324:Lepr
|
APN |
4 |
101625265 |
missense |
probably benign |
0.23 |
IGL01372:Lepr
|
APN |
4 |
101592774 |
missense |
possibly damaging |
0.67 |
IGL01626:Lepr
|
APN |
4 |
101590731 |
missense |
probably benign |
0.10 |
IGL01733:Lepr
|
APN |
4 |
101622279 |
missense |
probably benign |
0.00 |
IGL01815:Lepr
|
APN |
4 |
101671987 |
missense |
possibly damaging |
0.49 |
IGL01899:Lepr
|
APN |
4 |
101637184 |
missense |
possibly damaging |
0.86 |
IGL02138:Lepr
|
APN |
4 |
101625264 |
missense |
probably damaging |
0.98 |
IGL02161:Lepr
|
APN |
4 |
101602875 |
missense |
probably damaging |
0.97 |
IGL02653:Lepr
|
APN |
4 |
101622141 |
missense |
probably benign |
0.44 |
IGL02735:Lepr
|
APN |
4 |
101639835 |
missense |
probably damaging |
1.00 |
IGL03035:Lepr
|
APN |
4 |
101622177 |
missense |
probably damaging |
1.00 |
IGL03083:Lepr
|
APN |
4 |
101671876 |
nonsense |
probably null |
|
IGL03160:Lepr
|
APN |
4 |
101622103 |
missense |
probably damaging |
1.00 |
aufsetzigen
|
UTSW |
4 |
101609372 |
missense |
probably damaging |
1.00 |
beastly
|
UTSW |
4 |
101671788 |
missense |
probably benign |
|
business_class
|
UTSW |
4 |
101622069 |
missense |
probably damaging |
1.00 |
cherub
|
UTSW |
4 |
101625259 |
missense |
probably benign |
0.25 |
clodhopper
|
UTSW |
4 |
101622487 |
splice site |
probably null |
|
donner
|
UTSW |
4 |
101672398 |
missense |
probably damaging |
1.00 |
fluffy
|
UTSW |
4 |
101649220 |
missense |
probably damaging |
1.00 |
giant
|
UTSW |
4 |
101622349 |
critical splice donor site |
probably null |
|
gordo
|
UTSW |
4 |
101622502 |
missense |
probably damaging |
0.97 |
Immunoglutton
|
UTSW |
4 |
101622498 |
splice site |
probably benign |
|
Jumbo_shrimp
|
UTSW |
4 |
101622151 |
nonsense |
probably null |
|
lowleaning
|
UTSW |
4 |
101671588 |
splice site |
probably null |
|
odd
|
UTSW |
4 |
101585271 |
splice site |
probably benign |
|
R0140_Lepr_245
|
UTSW |
4 |
101625264 |
missense |
probably damaging |
1.00 |
well-upholstered
|
UTSW |
4 |
101630155 |
synonymous |
probably benign |
|
worldly
|
UTSW |
4 |
101625425 |
missense |
possibly damaging |
0.96 |
PIT4651001:Lepr
|
UTSW |
4 |
101649194 |
missense |
probably damaging |
1.00 |
PIT4696001:Lepr
|
UTSW |
4 |
101637180 |
missense |
probably benign |
0.10 |
R0140:Lepr
|
UTSW |
4 |
101625264 |
missense |
probably damaging |
1.00 |
R0197:Lepr
|
UTSW |
4 |
101609349 |
missense |
possibly damaging |
0.64 |
R0279:Lepr
|
UTSW |
4 |
101607541 |
missense |
probably benign |
0.05 |
R0487:Lepr
|
UTSW |
4 |
101625290 |
nonsense |
probably null |
|
R0498:Lepr
|
UTSW |
4 |
101602889 |
missense |
probably benign |
0.01 |
R0506:Lepr
|
UTSW |
4 |
101630207 |
splice site |
probably benign |
|
R0512:Lepr
|
UTSW |
4 |
101671901 |
missense |
possibly damaging |
0.87 |
R0512:Lepr
|
UTSW |
4 |
101649216 |
missense |
probably damaging |
1.00 |
R0726:Lepr
|
UTSW |
4 |
101622131 |
missense |
probably benign |
0.01 |
R1054:Lepr
|
UTSW |
4 |
101639793 |
missense |
probably damaging |
0.97 |
R1109:Lepr
|
UTSW |
4 |
101628552 |
missense |
probably damaging |
1.00 |
R1398:Lepr
|
UTSW |
4 |
101649216 |
missense |
probably damaging |
1.00 |
R1464:Lepr
|
UTSW |
4 |
101592878 |
missense |
probably benign |
0.08 |
R1464:Lepr
|
UTSW |
4 |
101592878 |
missense |
probably benign |
0.08 |
R1519:Lepr
|
UTSW |
4 |
101646541 |
missense |
probably damaging |
0.97 |
R1602:Lepr
|
UTSW |
4 |
101602842 |
missense |
possibly damaging |
0.94 |
R1830:Lepr
|
UTSW |
4 |
101592874 |
missense |
probably damaging |
1.00 |
R1850:Lepr
|
UTSW |
4 |
101590620 |
missense |
possibly damaging |
0.67 |
R1918:Lepr
|
UTSW |
4 |
101630033 |
missense |
probably benign |
0.08 |
R1928:Lepr
|
UTSW |
4 |
101639927 |
splice site |
probably benign |
|
R2099:Lepr
|
UTSW |
4 |
101630185 |
missense |
probably damaging |
1.00 |
R2102:Lepr
|
UTSW |
4 |
101630178 |
missense |
possibly damaging |
0.95 |
R2175:Lepr
|
UTSW |
4 |
101622576 |
missense |
probably benign |
0.01 |
R2254:Lepr
|
UTSW |
4 |
101672309 |
missense |
probably benign |
0.26 |
R2396:Lepr
|
UTSW |
4 |
101590725 |
missense |
probably benign |
0.19 |
R2508:Lepr
|
UTSW |
4 |
101648093 |
missense |
probably damaging |
0.98 |
R2571:Lepr
|
UTSW |
4 |
101625369 |
missense |
possibly damaging |
0.96 |
R3790:Lepr
|
UTSW |
4 |
101648111 |
splice site |
probably benign |
|
R3882:Lepr
|
UTSW |
4 |
101672462 |
missense |
probably damaging |
1.00 |
R3933:Lepr
|
UTSW |
4 |
101622498 |
splice site |
probably benign |
|
R4211:Lepr
|
UTSW |
4 |
101590611 |
missense |
probably benign |
0.19 |
R4343:Lepr
|
UTSW |
4 |
101622349 |
critical splice donor site |
probably null |
|
R4345:Lepr
|
UTSW |
4 |
101622349 |
critical splice donor site |
probably null |
|
R4544:Lepr
|
UTSW |
4 |
101625425 |
missense |
possibly damaging |
0.96 |
R4546:Lepr
|
UTSW |
4 |
101671838 |
missense |
probably benign |
0.35 |
R4724:Lepr
|
UTSW |
4 |
101622562 |
nonsense |
probably null |
|
R4797:Lepr
|
UTSW |
4 |
101637244 |
missense |
possibly damaging |
0.90 |
R4860:Lepr
|
UTSW |
4 |
101646534 |
missense |
probably benign |
0.14 |
R4860:Lepr
|
UTSW |
4 |
101646534 |
missense |
probably benign |
0.14 |
R4929:Lepr
|
UTSW |
4 |
101672314 |
missense |
probably benign |
0.00 |
R4939:Lepr
|
UTSW |
4 |
101590635 |
missense |
possibly damaging |
0.78 |
R5377:Lepr
|
UTSW |
4 |
101672216 |
missense |
possibly damaging |
0.71 |
R5520:Lepr
|
UTSW |
4 |
101602734 |
missense |
probably benign |
0.00 |
R5966:Lepr
|
UTSW |
4 |
101649324 |
intron |
probably benign |
|
R6092:Lepr
|
UTSW |
4 |
101649220 |
missense |
probably damaging |
1.00 |
R6130:Lepr
|
UTSW |
4 |
101622569 |
missense |
probably damaging |
0.99 |
R6168:Lepr
|
UTSW |
4 |
101592789 |
missense |
probably damaging |
0.99 |
R6232:Lepr
|
UTSW |
4 |
101671588 |
splice site |
probably null |
|
R6380:Lepr
|
UTSW |
4 |
101622151 |
nonsense |
probably null |
|
R6427:Lepr
|
UTSW |
4 |
101631454 |
missense |
possibly damaging |
0.47 |
R6428:Lepr
|
UTSW |
4 |
101637295 |
missense |
probably damaging |
1.00 |
R6641:Lepr
|
UTSW |
4 |
101622502 |
missense |
probably damaging |
0.97 |
R6650:Lepr
|
UTSW |
4 |
101672398 |
missense |
probably damaging |
1.00 |
R6859:Lepr
|
UTSW |
4 |
101622487 |
splice site |
probably null |
|
R7023:Lepr
|
UTSW |
4 |
101646484 |
missense |
probably damaging |
1.00 |
R7145:Lepr
|
UTSW |
4 |
101609394 |
missense |
probably benign |
0.00 |
R7174:Lepr
|
UTSW |
4 |
101607535 |
missense |
probably benign |
0.01 |
R7179:Lepr
|
UTSW |
4 |
101602856 |
missense |
probably benign |
0.06 |
R7189:Lepr
|
UTSW |
4 |
101671961 |
missense |
probably benign |
0.00 |
R7426:Lepr
|
UTSW |
4 |
101602853 |
missense |
probably benign |
0.03 |
R7531:Lepr
|
UTSW |
4 |
101609372 |
missense |
probably damaging |
1.00 |
R7620:Lepr
|
UTSW |
4 |
101609270 |
missense |
probably benign |
0.41 |
R7804:Lepr
|
UTSW |
4 |
101639783 |
missense |
probably damaging |
1.00 |
R8022:Lepr
|
UTSW |
4 |
101639754 |
missense |
probably benign |
0.32 |
R8142:Lepr
|
UTSW |
4 |
101622616 |
missense |
possibly damaging |
0.93 |
R8227:Lepr
|
UTSW |
4 |
101628559 |
missense |
probably damaging |
0.99 |
R8426:Lepr
|
UTSW |
4 |
101671841 |
missense |
probably benign |
0.12 |
R8447:Lepr
|
UTSW |
4 |
101671688 |
missense |
probably benign |
0.08 |
R8531:Lepr
|
UTSW |
4 |
101622612 |
missense |
probably damaging |
1.00 |
R8682:Lepr
|
UTSW |
4 |
101649269 |
missense |
probably benign |
0.00 |
R8897:Lepr
|
UTSW |
4 |
101649233 |
missense |
probably damaging |
0.98 |
R9096:Lepr
|
UTSW |
4 |
101631418 |
missense |
possibly damaging |
0.95 |
R9177:Lepr
|
UTSW |
4 |
101602798 |
nonsense |
probably null |
|
R9241:Lepr
|
UTSW |
4 |
101671788 |
missense |
probably benign |
|
R9604:Lepr
|
UTSW |
4 |
101590473 |
missense |
probably benign |
0.01 |
R9711:Lepr
|
UTSW |
4 |
101592851 |
nonsense |
probably null |
|
X0026:Lepr
|
UTSW |
4 |
101590524 |
missense |
possibly damaging |
0.47 |
Z1176:Lepr
|
UTSW |
4 |
101602811 |
missense |
probably damaging |
0.99 |
Z1177:Lepr
|
UTSW |
4 |
101592792 |
missense |
probably damaging |
1.00 |
|
Mode of Inheritance |
Autosomal Recessive |
Local Stock | Live Mice, Sperm, gDNA |
MMRRC Submission |
038250-MU
|
Last Updated |
2019-09-04 9:47 PM
by Diantha La Vine
|
Record Created |
2015-01-08 10:53 PM
by Jeff SoRelle
|
Record Posted |
2015-02-10 |
Phenotypic Description |
The paleo phenotype was identified among N-Nitroso-N-ethylurea (ENU)-mutagenized G3 mice of the pedigree R1602, some of which showed increased body weights compared to wild-type mice (Figure 1).
|
Nature of Mutation |
Whole exome HiSeq sequencing of the G1 grandsire identified 47 mutations. The body weight phenotype was linked to a mutation in Lepr: a T to A transversion at base pair 101,745,645 (v38) on chromosome 4, or base pair 28,239 in the GenBank genomic region NC_000070. Linkage was found with a recessive model of inheritance (P = 1.518 x 10-20), wherein four variant homozygotes departed phenotypically from nine homozygous reference mice and 23 heterozygous mice (Figure 2). A substantial semidominant effect was observed in most of the assays but the mutation is preponderantly recessive. The mutation corresponds to residue 1,181 in the mRNA sequence NM_146146 within exon 5 of 19 total exons.
1165 AACTACGCTCTTCTGATGTATTTGGAAATCACA
205 -N--Y--A--L--L--M--Y--L--E--I--T-
|
The mutated nucleotide is indicated in red. The mutation results in a methionine (M) to lysine (K) substitution at position 210 (M210K) in the Lepr protein, and is strongly predicted by Polyphen-2 to cause loss of function (score = 0.938). |
Illustration of Mutations in
Gene & Protein |
|
---|
Protein Prediction |
The Lepr or obr gene encodes an 1162 amino acid protein that is the receptor for leptin, a four-helical cytokine-like hormone produced primarily by adipocytes [Figure 3; (1;2)]. The leptin receptor is a member of the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT (signal transducer and activator of transcription) proteins (see domino for more information on STAT signaling). Six isoforms of the leptin receptor are generated by alternative splicing; each isoform, with the exception of a soluble isoform (OB-Re) are single-pass membrane-spanning proteins differing only in the sequences of their C-terminal intracellular domains. The extracellular portion of the human leptin receptor contains two CK domains that contain conserved cysteine-containing motifs (amino acids 62-178 and amino acids 428-535), four domains that contain a fibronectin type III (FNIII) fold (amino acids 235-327, 536-635, 636-731, and amino acids 732-841), and a domain that has an Ig-like fold (amino acids 328-427). The first CK domain and the first FNIII domain form the cytokine receptor homology module 1 (CRH1), while the second CK domain and remaining FNIII domains form the cytokine receptor homology module 2. The paleo mutation is a missense mutation at amino acid 210 (M210K). Residue 210 is within CRH1 in an undefined region between the cysteine-containing CK motif and the fibronectin III (FNIII) domains. The function of CRH1 remains to be determined. Please see the record for Business class for more information on Lepr.
|
Putative Mechanism | Leptin, a systemic hormone, regulates multiple functions of the body including energy utilization and storage, various endocrine axes, bone metabolism, thermoregulation, angiogenesis, immunity and inflammation by binding to the long form of the leptin receptor (OB-Rb) and subsequent initiation of various signal transduction pathways [reviewed in (3-5)]. It is primarily produced by adipocytes in proportion to fat stores, but can also be produced by placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach, mammary epithelial cells, bone marrow, pituitary and liver (6). Humans and other animals deficient for leptin or its receptor, exhibit hyperphagia and low metabolism that results in obesity and insulin resistance [OMIM #614963; (2;7;8)]. Similar to other Lepr mouse models, the paleo mice exhibit obesity. The phenotype of the paleo mice indicates that the Leprpaleo protein exhibits loss of function.
|
Primers |
PCR Primer
paleo_pcr_F: GCCCTTGCTTATGCTACCTTGACAG
paleo_pcr_R: AGGGTCTCCAGCCTCTATGCTAATC
Sequencing Primer
paleo_seq_F: ATGCTACCTTGACAGTCAGTC
paleo_seq_R: CTTACCAACAAGCATGGGCT
|
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 663 nucleotides is amplified (chromosome 4, + strand):
1 gcccttgctt atgctacctt gacagtcagt ctccataccc atcttatatt ttgttcttat 61 atttgaatat aggcctgaag tcatagatga ttcgcctctg cccccactga aagacagctt 121 tcagactgtc caatgcaact gcagtcttcg gggatgtgaa tgtcatgtgc cggtacccag 181 agccaaactc aactacgctc ttctgatgta tttggaaatc acatctgccg gtgtgagttt 241 tcagtcacct ctgatgtcac tgcagcccat gcttgttggt aagttgcact tcagagtgac 301 agtgacccta aaaaaaaaaa tcaatcatgc aaagctgttg aaaggttact tgtgggttaa 361 agattttcac tggcttacat cactgtgatc actgctgaaa aacatggcta gtcctagggt 421 gttattggca gcttctccac atgttcatag tagtcaacat ctctaacatt agcactgaaa 481 tggtcttttg aagcagctgg ggctccttta agtcttggat ttagtgaatg gatgtgtatt 541 gtttgattac catctgttta tatcatagtt aactattttt gaaaattatt aaaaacctat 601 ttctccaata aatacaactt agaattcatg tgtgcaggga ttagcataga ggctggagac 661 cct
Primer binding sites are underlined and the sequencing primers are highlighted; the mutated nucleotide is shown in red. |
References | 1. Zhang, F., Basinski, M. B., Beals, J. M., Briggs, S. L., Churgay, L. M., Clawson, D. K., DiMarchi, R. D., Furman, T. C., Hale, J. E., Hsiung, H. M., Schoner, B. E., Smith, D. P., Zhang, X. Y., Wery, J. P., and Schevitz, R. W. (1997) Crystal Structure of the Obese Protein Leptin-E100. Nature. 387, 206-209.
2. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. M. (1994) Positional Cloning of the Mouse Obese Gene and its Human Homologue. Nature. 372, 425-432.
4. Malendowicz, L. K., Rucinski, M., Belloni, A. S., Ziolkowska, A., and Nussdorfer, G. G. (2007) Leptin and the Regulation of the Hypothalamic-Pituitary-Adrenal Axis. Int Rev Cytol. 263, 63-102.
7. Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., Moore, K. J., Breitbart, R. E., Duyk, G. M., Tepper, R. I., and Morgenstern, J. P. (1996) Evidence that the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db/db Mice. Cell. 84, 491-495.
8. Farooqi, I. S., Wangensteen, T., Collins, S., Kimber, W., Matarese, G., Keogh, J. M., Lank, E., Bottomley, B., Lopez-Fernandez, J., Ferraz-Amaro, I., Dattani, M. T., Ercan, O., Myhre, A. G., Retterstol, L., Stanhope, R., Edge, J. A., McKenzie, S., Lessan, N., Ghodsi, M., De, R.,V, Perna, F., Fontana, S., Barroso, I., Undlien, D. E., and O'Rahilly, S. (2007) Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor. N Engl J Med. 356, 237-247.
|
Science Writers | Anne Murray |
Illustrators | Peter Jurek |
Authors | Jeff SoRelle, Zhe Chen, Noelle Hutchins |