Phenotypic Mutation 'dew' (pdf version)
Alleledew
Mutation Type nonsense
Chromosome11
Coordinate34,198,636 bp (GRCm39)
Base Change G ⇒ A (forward strand)
Gene Dock2
Gene Name dedicator of cyto-kinesis 2
Synonym(s) CED-5, Hch, MBC
Chromosomal Location 34,176,815-34,674,719 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 CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. [provided by RefSeq, Oct 2016]
PHENOTYPE: Homozygous mutants are defective in the migration of T and B lympohcytes in response to chemokines, and thus display immune defects such as lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_033374; MGI: 2149010

MappedYes 
Amino Acid Change Glutamine changed to Stop codon
Institutional SourceBeutler Lab
Gene Model not available
AlphaFold Q8C3J5
SMART Domains Protein: ENSMUSP00000090884
Gene: ENSMUSG00000020143
AA Change: Q1439*

DomainStartEndE-ValueType
SH3 11 68 1.22e-11 SMART
Pfam:DOCK_N 71 414 2e-113 PFAM
Pfam:DOCK-C2 419 616 1e-60 PFAM
Pfam:DHR-2 1114 1614 6.3e-96 PFAM
low complexity region 1691 1706 N/A INTRINSIC
low complexity region 1793 1800 N/A INTRINSIC
Predicted Effect probably null
Meta Mutation Damage Score Not available question?
Is this an essential gene? Non Essential (E-score: 0.000) question?
Phenotypic Category Autosomal Recessive
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance  
Alleles Listed at MGI

All alleles(18) : Targeted(4) Gene trapped(11) Spontaneous(1) Chemically induced(2)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00334:Dock2 APN 11 34595488 missense probably damaging 1.00
IGL00469:Dock2 APN 11 34179603 splice site probably benign
IGL01061:Dock2 APN 11 34596653 missense probably damaging 1.00
IGL01319:Dock2 APN 11 34589617 missense possibly damaging 0.61
IGL01451:Dock2 APN 11 34260390 missense probably damaging 1.00
IGL01490:Dock2 APN 11 34596608 missense probably damaging 0.97
IGL01601:Dock2 APN 11 34189528 critical splice donor site probably null
IGL01800:Dock2 APN 11 34647100 missense probably damaging 1.00
IGL01804:Dock2 APN 11 34212433 missense probably benign 0.01
IGL01823:Dock2 APN 11 34212391 missense probably damaging 1.00
IGL01829:Dock2 APN 11 34596668 missense probably damaging 0.98
IGL01830:Dock2 APN 11 34582744 nonsense probably null
IGL01835:Dock2 APN 11 34260435 missense possibly damaging 0.51
IGL01845:Dock2 APN 11 34599692 missense probably benign 0.02
IGL01953:Dock2 APN 11 34623183 missense probably benign 0.28
IGL01989:Dock2 APN 11 34218053 missense probably benign
IGL02081:Dock2 APN 11 34204355 missense probably benign
IGL02105:Dock2 APN 11 34605352 missense probably damaging 1.00
IGL02153:Dock2 APN 11 34180670 missense probably benign 0.01
IGL02170:Dock2 APN 11 34217949 missense probably damaging 1.00
IGL02344:Dock2 APN 11 34622337 missense probably damaging 0.98
IGL02389:Dock2 APN 11 34589567 splice site probably benign
IGL02409:Dock2 APN 11 34451204 missense probably benign 0.00
IGL02472:Dock2 APN 11 34199801 missense probably benign 0.00
IGL02625:Dock2 APN 11 34451168 critical splice donor site probably null
IGL02929:Dock2 APN 11 34218048 missense probably damaging 1.00
IGL02951:Dock2 APN 11 34260448 unclassified probably benign
IGL02999:Dock2 APN 11 34583086 missense probably damaging 0.99
IGL03165:Dock2 APN 11 34578360 missense probably damaging 0.99
Arches UTSW 11 34580587 missense probably damaging 1.00
capitol_reef UTSW 11 34244170 critical splice acceptor site probably null
Croesus UTSW 11 34611854 missense probably damaging 1.00
denali UTSW 11 34179472 critical splice donor site probably null
Dinghy UTSW 11 34212460 missense possibly damaging 0.70
Dry UTSW 11 34181652 missense possibly damaging 0.79
frazz UTSW 11 34198572 critical splice donor site probably benign
frizz UTSW 11 34208184 splice site probably benign
gildenstern UTSW 11 34623166 critical splice donor site probably null
godsgrace UTSW 11 34586280 missense probably damaging 1.00
Harborside UTSW 11 34212445 missense probably benign
Landing UTSW 11 34605328 missense possibly damaging 0.83
latest UTSW 11 34647049 missense probably damaging 1.00
Launch UTSW 11 34206562 missense probably damaging 1.00
liaoning UTSW 11 34599620 missense probably damaging 1.00
lucre UTSW 11 34595436 frame shift probably null
midas UTSW 11 34244323 missense probably damaging 0.99
muelle UTSW 11 34578365 missense probably damaging 1.00
narrowest UTSW 11 34232652 missense probably damaging 0.98
pier UTSW 11 34580593 missense probably damaging 1.00
Plank UTSW 11 34674622 missense possibly damaging 0.51
resplendent UTSW 11 34618287 nonsense probably null
riches UTSW 11 34579279 critical splice donor site probably null
skiff UTSW 11 34212388 missense probably null 0.80
Slip UTSW 11 34244286 missense probably benign 0.25
toothskin UTSW 11 34414922 missense probably damaging 1.00
Touch UTSW 11 34223750 missense possibly damaging 0.95
wassup UTSW 11 34453413 missense probably damaging 1.00
Wharf UTSW 11 34623198 missense possibly damaging 0.81
BB009:Dock2 UTSW 11 34217998 missense probably benign 0.00
BB019:Dock2 UTSW 11 34217998 missense probably benign 0.00
IGL03052:Dock2 UTSW 11 34182853 missense probably benign 0.01
PIT4377001:Dock2 UTSW 11 34611835 missense probably benign 0.02
R0006:Dock2 UTSW 11 34262453 unclassified probably benign
R0012:Dock2 UTSW 11 34674622 missense possibly damaging 0.51
R0063:Dock2 UTSW 11 34647111 critical splice acceptor site probably null
R0063:Dock2 UTSW 11 34647111 critical splice acceptor site probably null
R0116:Dock2 UTSW 11 34579392 intron probably benign
R0149:Dock2 UTSW 11 34388327 missense probably damaging 1.00
R0361:Dock2 UTSW 11 34388327 missense probably damaging 1.00
R0462:Dock2 UTSW 11 34218052 missense possibly damaging 0.74
R0471:Dock2 UTSW 11 34579380 missense probably benign 0.30
R0538:Dock2 UTSW 11 34595545 splice site probably benign
R0543:Dock2 UTSW 11 34244325 missense probably damaging 1.00
R0660:Dock2 UTSW 11 34198621 missense probably damaging 1.00
R0676:Dock2 UTSW 11 34586063 missense probably damaging 0.99
R0722:Dock2 UTSW 11 34414970 splice site probably benign
R0801:Dock2 UTSW 11 34599620 missense probably damaging 1.00
R1110:Dock2 UTSW 11 34206535 missense possibly damaging 0.78
R1171:Dock2 UTSW 11 34586068 missense probably damaging 1.00
R1387:Dock2 UTSW 11 34223309 splice site probably benign
R1445:Dock2 UTSW 11 34189705 missense probably benign
R1494:Dock2 UTSW 11 34232761 nonsense probably null
R1589:Dock2 UTSW 11 34597288 missense probably damaging 0.99
R1597:Dock2 UTSW 11 34595474 missense probably benign 0.00
R1629:Dock2 UTSW 11 34212480 splice site probably null
R1749:Dock2 UTSW 11 34182767 critical splice donor site probably null
R1888:Dock2 UTSW 11 34598169 missense probably damaging 1.00
R1888:Dock2 UTSW 11 34598169 missense probably damaging 1.00
R1899:Dock2 UTSW 11 34244286 missense probably benign 0.25
R1924:Dock2 UTSW 11 34414934 missense possibly damaging 0.69
R2031:Dock2 UTSW 11 34618297 splice site probably benign
R2045:Dock2 UTSW 11 34244106 splice site probably null
R2098:Dock2 UTSW 11 34609832 missense probably damaging 0.99
R2098:Dock2 UTSW 11 34216279 missense probably benign 0.16
R2129:Dock2 UTSW 11 34618242 missense probably damaging 1.00
R2147:Dock2 UTSW 11 34179472 critical splice donor site probably null
R2149:Dock2 UTSW 11 34179472 critical splice donor site probably null
R2150:Dock2 UTSW 11 34179472 critical splice donor site probably null
R2176:Dock2 UTSW 11 34586044 missense probably benign 0.00
R2230:Dock2 UTSW 11 34244323 missense probably damaging 0.99
R2508:Dock2 UTSW 11 34262485 missense probably benign 0.04
R2875:Dock2 UTSW 11 34609712 missense probably damaging 1.00
R2885:Dock2 UTSW 11 34580593 missense probably damaging 1.00
R2910:Dock2 UTSW 11 34182910 splice site probably benign
R3081:Dock2 UTSW 11 34181610 missense probably benign
R3418:Dock2 UTSW 11 34580587 missense probably damaging 1.00
R3552:Dock2 UTSW 11 34611787 missense probably benign 0.22
R3731:Dock2 UTSW 11 34599722 missense probably damaging 1.00
R3846:Dock2 UTSW 11 34623198 missense possibly damaging 0.81
R4135:Dock2 UTSW 11 34605328 missense possibly damaging 0.83
R4598:Dock2 UTSW 11 34189536 missense probably damaging 1.00
R4599:Dock2 UTSW 11 34189536 missense probably damaging 1.00
R4715:Dock2 UTSW 11 34244118 missense probably damaging 1.00
R4722:Dock2 UTSW 11 34586298 missense probably damaging 1.00
R4742:Dock2 UTSW 11 34244170 critical splice acceptor site probably null
R4830:Dock2 UTSW 11 34223767 splice site probably null
R4884:Dock2 UTSW 11 34216248 missense probably damaging 1.00
R4990:Dock2 UTSW 11 34586078 missense probably damaging 1.00
R5334:Dock2 UTSW 11 34178643 missense probably benign 0.00
R5570:Dock2 UTSW 11 34618233 missense probably damaging 1.00
R5602:Dock2 UTSW 11 34204391 missense probably benign 0.16
R5681:Dock2 UTSW 11 34199836 missense probably benign 0.06
R5809:Dock2 UTSW 11 34212445 missense probably benign
R5860:Dock2 UTSW 11 34206562 missense probably damaging 1.00
R6111:Dock2 UTSW 11 34599614 missense probably damaging 0.99
R6155:Dock2 UTSW 11 34244123 missense probably benign 0.06
R6156:Dock2 UTSW 11 34197789 missense possibly damaging 0.51
R6173:Dock2 UTSW 11 34212388 missense probably null 0.80
R6182:Dock2 UTSW 11 34179476 missense probably damaging 0.97
R6188:Dock2 UTSW 11 34453396 missense probably damaging 0.98
R6191:Dock2 UTSW 11 34181652 missense possibly damaging 0.79
R6283:Dock2 UTSW 11 34598152 missense probably damaging 0.99
R6395:Dock2 UTSW 11 34182874 missense probably damaging 1.00
R6465:Dock2 UTSW 11 34453413 missense probably damaging 1.00
R6500:Dock2 UTSW 11 34312822 missense possibly damaging 0.76
R6561:Dock2 UTSW 11 34578365 missense probably damaging 1.00
R6745:Dock2 UTSW 11 34596670 missense probably damaging 1.00
R6745:Dock2 UTSW 11 34596669 missense probably damaging 1.00
R6880:Dock2 UTSW 11 34579279 critical splice donor site probably null
R6913:Dock2 UTSW 11 34647049 missense probably damaging 1.00
R6997:Dock2 UTSW 11 34414922 missense probably damaging 1.00
R7057:Dock2 UTSW 11 34586044 missense probably benign 0.00
R7057:Dock2 UTSW 11 34177684 missense probably benign 0.10
R7134:Dock2 UTSW 11 34260363 missense probably benign 0.03
R7188:Dock2 UTSW 11 34189675 missense possibly damaging 0.87
R7239:Dock2 UTSW 11 34181677 missense probably benign 0.00
R7247:Dock2 UTSW 11 34605340 nonsense probably null
R7250:Dock2 UTSW 11 34586120 missense probably damaging 1.00
R7250:Dock2 UTSW 11 34586032 missense probably benign 0.01
R7271:Dock2 UTSW 11 34223750 missense possibly damaging 0.95
R7284:Dock2 UTSW 11 34180672 missense probably benign 0.01
R7397:Dock2 UTSW 11 34609816 missense probably benign 0.00
R7464:Dock2 UTSW 11 34586105 missense probably damaging 0.99
R7512:Dock2 UTSW 11 34262542 missense possibly damaging 0.95
R7556:Dock2 UTSW 11 34611778 missense probably benign 0.43
R7663:Dock2 UTSW 11 34611854 missense probably damaging 1.00
R7779:Dock2 UTSW 11 34605282 missense probably benign 0.38
R7797:Dock2 UTSW 11 34232652 missense probably damaging 0.98
R7855:Dock2 UTSW 11 34223698 missense probably damaging 1.00
R7922:Dock2 UTSW 11 34598154 missense probably benign 0.29
R7932:Dock2 UTSW 11 34217998 missense probably benign 0.00
R8013:Dock2 UTSW 11 34596677 missense probably damaging 0.96
R8192:Dock2 UTSW 11 34623166 critical splice donor site probably null
R8244:Dock2 UTSW 11 34586280 missense probably damaging 1.00
R8307:Dock2 UTSW 11 34260362 missense possibly damaging 0.95
R8418:Dock2 UTSW 11 34609795 missense probably benign 0.01
R8460:Dock2 UTSW 11 34180825 critical splice acceptor site probably null
R8495:Dock2 UTSW 11 34181622 missense probably benign 0.14
R8556:Dock2 UTSW 11 34212457 missense possibly damaging 0.84
R8690:Dock2 UTSW 11 34618287 nonsense probably null
R8743:Dock2 UTSW 11 34223252 nonsense probably null
R8757:Dock2 UTSW 11 34586067 missense probably benign 0.13
R8759:Dock2 UTSW 11 34586067 missense probably benign 0.13
R8793:Dock2 UTSW 11 34451215 missense probably benign 0.00
R8882:Dock2 UTSW 11 34595436 frame shift probably null
R8885:Dock2 UTSW 11 34260396 missense probably benign 0.01
R8943:Dock2 UTSW 11 34599646 missense possibly damaging 0.63
R9171:Dock2 UTSW 11 34589670 missense probably benign 0.12
R9182:Dock2 UTSW 11 34260398 missense possibly damaging 0.51
R9203:Dock2 UTSW 11 34622366 missense possibly damaging 0.92
R9310:Dock2 UTSW 11 34244139 missense possibly damaging 0.71
R9388:Dock2 UTSW 11 34212460 missense possibly damaging 0.70
R9490:Dock2 UTSW 11 34589582 missense possibly damaging 0.90
R9568:Dock2 UTSW 11 34599638 missense possibly damaging 0.83
R9593:Dock2 UTSW 11 34178607 missense probably benign 0.34
R9694:Dock2 UTSW 11 34218054 missense probably benign
R9697:Dock2 UTSW 11 34204417 missense probably benign
R9753:Dock2 UTSW 11 34223673 missense possibly damaging 0.68
R9783:Dock2 UTSW 11 34208128 missense possibly damaging 0.83
X0017:Dock2 UTSW 11 34216271 missense probably benign 0.08
X0018:Dock2 UTSW 11 34182833 missense possibly damaging 0.65
X0058:Dock2 UTSW 11 34206564 missense probably damaging 1.00
X0066:Dock2 UTSW 11 34260357 missense possibly damaging 0.95
Z1088:Dock2 UTSW 11 34583209 missense probably damaging 1.00
Z1088:Dock2 UTSW 11 34388300 missense probably benign 0.14
Z1088:Dock2 UTSW 11 34586039 nonsense probably null
Z1176:Dock2 UTSW 11 34609751 missense probably benign 0.04
Z1177:Dock2 UTSW 11 34262553 missense possibly damaging 0.68
Mode of Inheritance Autosomal Recessive
Local Stock Live Mice, Sperm
MMRRC Submission 036803-MU
Last Updated 2019-05-21 7:40 PM by Diantha La Vine
Record Created 2010-10-11 7:39 PM by Carrie N. Arnold
Record Posted 2013-01-29
Other Mutations in This Stock Stock #: I2505 Run Code: SLD00273
Validation Efficiency: 113/115

GeneSubstitutionChr/LocMutationPredicted EffectZygosity
Obi1 T to A 14: 104,740,885 (GRCm39) probably benign Het
Rxrb T to C 17: 34,252,523 (GRCm39) probably benign Het
Zfp738 C to T 13: 67,821,186 (GRCm39) V64I probably benign Het
Phenotypic Description
Figure 1. The dew mouse was identified in a T-dependent Humoral Response Screen of N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice (red dots).

Figure 2. The dew mice (V7590, V7597, V7592, and V7594) do not exhibit a T-dependent IgG response.

Figure 3. CD4+ and CD8+ T cells are depleted in the dew mice (green bars). Other hematopoietic cell types are not significantly affected.

The dew mutation was identified in a T-dependent Humoral Response Screen of N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice (Figure 1).  The dew mice lack a T-dependent IgG response (Figure 2); the T-independent IgM response is normal. Fluorescence activated cell sorting (FACS) analysis determined that CD4+ and CD8+ T cells are depleted in the dew mice (Figure 3). 

Nature of Mutation

Whole genome sequencing of a homozygous dew mouse using the SOLiD technique identified a C to T transition at base pair 34148636 on Chromosome 11 in the GenBank genomic region NC_000077 encoding Dock2. The mutation corresponds to residue 4367 of the mRNA sequence NM_033374 in exon 43 (of 52).

4380 ACAAGTCTAATTATGTGCAAAAGTTCCACTACTCC

1433 Y--K--S--N--Y--V--Q--K--F--H--Y--S-

The mutated nucleotide is indicated in red lettering and results in substitution of glutamine (Q) 1439 for a premature stop codon.

Illustration of Mutations in
Gene & Protein
Protein Prediction
Figure 5. Domain structure of mouse DOCK2, a member of the DOCK A subfamily. DOCK A proteins contain an N-terminal SH3 domain. SH3-containing DOCK proteins have been shown to interact physically with the scaffolding proteins engulfment and cell motility protein 1 (ELMO1) and ELMO2, significantly promoting Rac activation. DHR-1 domain shares weak homology to the C2 domain. The large DHR-2 domain interacts with the nucleotide-free form of Rac. The dew mutation results in substitution of glutamine (Q) 1439 for a premature stop codon. This image is interactive. Other mutations found in DOCK2 are noted in red. Click on each mutation for more specific information.

The dew mutation results in a coding of a premature stop codon at amino acid 1439 within the catalytic DOCK homology region 2 (DHR-2), a domain essential for the interaction of Dock2 with GTPases [Figure 5(1;2)].

For more information on Dock2, see the record for frazz.

Primers Primers cannot be located by automatic search.
Genotyping
Figure. DNA sequencing trace of the Chr. + strand.
Dew 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
Dew(F): 5’- AGAAGACCCAGTAGACTTGTCACCC -3’
Dew(R): 5’- AATGCCAGAATTGCAAATGCCCAG -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               8
 
Primers for sequencing
Dew_seq(F): 5'- AGTAGACTTGTCACCCTATCTGG -3'
 

The following sequence of 415 nucleotides is amplified (Chr. 11: 34248432-34248846, GRCm38.; NC_000077):

agaagaccca gtagacttgt caccctatct gggatgtcca tgtagtattc actccctggc
tctggatcaa gctgccccca cctgtggttg gcagaggtgt gttctggttg ctgaagatgg
ctgaggaggg gattatactc acagcaaact cgttctctgg gtctaccttg cccctgcgca
caggcctgga gtagtggaac ttttgcacat aattagactt gtaaaagctg aaagacagaa
aggagtagaa gtttctggaa gccatgctac ccatccactg aaaccttaaa catcaggtct
ggcagggccc tggcagtggc atttcaaggt ctgagttggg gcttcataaa aagtgatttg
cacagggttg cagggtgatt tagaagccac cctgggcatt tgcaattctg gcatt

Primer binding sites are underlined; sequencing primer binding sites are highlighted in gray; the mutated nucleotide is indicated in red (G>A on Chr. + strand; C>T on sense strand).

References
Science Writers Anne Murray
Illustrators Katherine Timer
AuthorsCarrie Arnold, Elaine Pirie, Ming Zeng and Bruce Beutler