Incidental Mutation 'P0026:Elf3'
ID8227
Institutional Source Beutler Lab
Gene Symbol Elf3
Ensembl Gene ENSMUSG00000003051
Gene NameE74-like factor 3
SynonymsESX, jen, ESE-1
MMRRC Submission 038279-MU
Accession Numbers

Ncbi RefSeq: NM_001163131.1, NM_007921.3; MGI:1101781

Is this an essential gene? Probably essential (E-score: 0.882) question?
Stock #P0026 (G1)
Quality Score
Status Validated
Chromosome1
Chromosomal Location135253575-135258568 bp(-) (GRCm38)
Type of Mutationcritical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 135255973 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000139769 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000003135] [ENSMUST00000185752]
Predicted Effect probably null
Transcript: ENSMUST00000003135
SMART Domains Protein: ENSMUSP00000003135
Gene: ENSMUSG00000003051

DomainStartEndE-ValueType
SAM_PNT 67 151 6.32e-30 SMART
low complexity region 230 241 N/A INTRINSIC
AT_hook 264 276 1.29e0 SMART
ETS 292 379 6.11e-49 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000180981
Predicted Effect probably null
Transcript: ENSMUST00000185752
SMART Domains Protein: ENSMUSP00000139769
Gene: ENSMUSG00000003051

DomainStartEndE-ValueType
SAM_PNT 47 131 1.36e-29 SMART
low complexity region 210 221 N/A INTRINSIC
AT_hook 244 256 1.29e0 SMART
ETS 272 359 6.11e-49 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000188895
Meta Mutation Damage Score 0.9491 question?
Coding Region Coverage
  • 1x: 85.6%
  • 3x: 78.9%
  • 10x: 59.5%
  • 20x: 38.1%
Validation Efficiency 97% (63/65)
MGI Phenotype Strain: 2662485
Lethality: D11-D21
PHENOTYPE: About one third of mice homozygous for a reporter allele die at E11.5; over half of those born develop a wasted phenotype, lethargy and watery diarrhea and die during the first few weeks of life exhibiting dysmorphogenesis and altered differentiation of small intestinal epithelium. [provided by MGI curators]
Allele List at MGI

All alleles(3) : Targeted(3)

Other mutations in this stock
Total: 26 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abi2 A G 1: 60,453,723 N182D probably benign Het
Acad10 T C 5: 121,637,352 Y429C probably damaging Het
Aifm3 A T 16: 17,507,117 probably benign Het
Bud13 A G 9: 46,288,358 H339R probably benign Het
Cpa1 T A 6: 30,640,906 M132K probably damaging Het
Dapk1 T A 13: 60,718,149 probably benign Het
Dchs1 A T 7: 105,758,405 N2073K probably damaging Het
Dnah2 A T 11: 69,464,947 N2227K probably damaging Het
Dnpep C T 1: 75,308,685 V468I probably benign Het
Fam124a T G 14: 62,606,122 L360V probably damaging Het
Fam20a A T 11: 109,675,841 probably null Het
Fermt3 A G 19: 7,014,424 S140P probably damaging Het
Gm10440 T C 5: 54,356,169 noncoding transcript Het
Il12rb1 A G 8: 70,812,541 D167G probably damaging Het
Ints8 T A 4: 11,225,788 K590* probably null Het
Kcnu1 T C 8: 25,892,122 F500S probably damaging Het
Mrm3 T C 11: 76,247,500 V238A probably damaging Het
Rap1gap2 A G 11: 74,567,210 probably benign Het
Rusc2 T A 4: 43,415,840 V382E possibly damaging Het
Slc9a5 A G 8: 105,355,291 N216S probably damaging Het
Snx7 A T 3: 117,840,023 F63I probably damaging Het
Syne2 A G 12: 75,880,220 probably benign Het
Tenm4 T C 7: 96,874,527 Y1751H probably damaging Het
Trappc9 G A 15: 72,953,082 P366S probably damaging Het
Trim17 A G 11: 58,971,258 D372G possibly damaging Het
Zfp354a G A 11: 51,061,498 G85R probably null Het
Other mutations in Elf3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02141:Elf3 APN 1 135257707 missense possibly damaging 0.94
IGL02470:Elf3 APN 1 135255012 missense probably damaging 1.00
IGL03018:Elf3 APN 1 135256065 missense possibly damaging 0.62
IGL03252:Elf3 APN 1 135254953 missense probably damaging 1.00
R0087:Elf3 UTSW 1 135257137 missense probably damaging 1.00
R1842:Elf3 UTSW 1 135256793 missense possibly damaging 0.65
R1897:Elf3 UTSW 1 135257137 missense probably damaging 1.00
R2081:Elf3 UTSW 1 135257076 missense probably benign 0.12
R4049:Elf3 UTSW 1 135254277 missense probably benign 0.21
R4467:Elf3 UTSW 1 135256844 missense probably damaging 1.00
R4630:Elf3 UTSW 1 135256740 intron probably benign
R4715:Elf3 UTSW 1 135257752 missense probably damaging 1.00
R4923:Elf3 UTSW 1 135256735 intron probably benign
R5226:Elf3 UTSW 1 135257239 missense probably benign 0.07
R5422:Elf3 UTSW 1 135255040 missense probably damaging 0.98
R5706:Elf3 UTSW 1 135256482 missense probably benign 0.01
R7115:Elf3 UTSW 1 135257118 missense probably damaging 1.00
R7644:Elf3 UTSW 1 135256506 missense possibly damaging 0.89
R7855:Elf3 UTSW 1 135254352 missense probably damaging 1.00
R7938:Elf3 UTSW 1 135254352 missense probably damaging 1.00
Protein Function and Prediction

Elf3 encodes an E26 transformation-specific (ETS) transcription factor.  The Ets transcription factors are often mediators of extracellular signaling pathways that regulate cell proliferation, differentiation, apoptosis, and cell-cell/cell-matrix interactions (1;2).  Elf3 is involved in embryonic epithelial differentiation (3). Elf3 controls intestinal epithelial differentiation during development by regulating the expression of TGFβRII in epithelial cells [(4;5); reviewed in (6)]. Elf3 is also involved in mediating vascular inflammation after induction by inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage; induction is mediated by by NF-κB transactivation of the Elf3 promoter. Elf3 can bind to the p50 subunit of NF-κB, an ESE-1-binding site within the NOS2 promoter has been identified, and Elf3 is also a transcriptional mediator of angiopoietin-1 in inflammation (7;8).  In addition, Elf3 regulates allergic airway inflammation by regulating DC-driven T cell differentiation (9). Other proposed roles of Elf3 are terminal differentiation of the epidermal skin epithelium, mammary gland development and breast cancer, and lung development, regeneration, and cancer [reviewed in (10)].

Expression/Localization

Elf3 is highly expressed in epithelial-rich tissues such as stomach, small intestine, colon, pancreas, trachea, lung, kidney, salivary gland, prostate gland, mammary gland, uterus, and skin (11;12).

Background

Elf3tm1Pjh/tm1Pjh; MGI:2662485

involves: 129S4/SvJae * C57BL/6

About one third of mice homozygous for a reporter allele die at E11.5; over half of those born develop a wasted phenotype, lethargy and watery diarrhea and die during the first few weeks of life exhibiting dysmorphogenesis and altered differentiation of small intestinal epithelium (3).  The impaired enterocyte and goblet cell differentiation can be rescued by transgenic TGFβRII expression in the intestinal epithelium (4) via direct stimulation of TGFβRII promotor activity (5).

 

Elf3−/− mice: not clear if same model as above; not indicated in publication

Elf3−/− mice were impaired in Th17 induction after epicutaneous sensitization and airway challenge with OVA (9). After epicutaneous sensitization, Elf3−/− mice have impaired Th1 differentiation, which subsequently promotes Th2 differentiation (9).  IL-6 production in the OVA-challenged and -sensitized Elf3−/− mice is impaired (9).  These mice exhibit increased maturation and migration of dendritic cells upon OVA sensitization (9).

References
Posted On2012-11-20
Science WriterAnne Murray