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Mouse Tnik Conditional Knockout Project (CRISPR/Cas9)

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Mouse Tnik Conditional Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Tnik Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Tnik conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Tnik gene (NCBI Reference Sequence: NM_026910 ; Ensembl: ENSMUSG00000027692 ) is located on Mouse chromosome 3. 33 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 33 (Transcript: ENSMUST00000160307). Exon 7 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Tnik gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-433L13 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a knock-out allele exhibit impaired postsynaptic signaling and cognitive function. Exon 7 starts from about 12.48% of the coding region. The knockout of Exon 7 will result in frameshift of the gene. The size of intron 6 for 5'-loxP site insertion: 2463 bp, and the size of intron 7 for 3'-loxP site insertion: 12829 bp. The size of effective cKO region: ~631 bp. The cKO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 7 33 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Tnik Homology arm cKO region loxP site Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the GC Content Distribution Window size: 300 bp Sequence 12 Summary: Full Length(7131bp) | A(28.45% 2029) | C(20.47% 1460) | T(29.84% 2128) | G(21.23% 1514) Note: The sequence of homologous arms and cKO region is analyzed to determine the GC content. No significant high GC-content region is found. So this region is suitable for PCR screening or sequencing analysis. Page 3 of 8 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr3 + 28538719 28541718 3000 browser details YourSeq 117 2755 2997 3000 83.4% chr16 - 84953774 84954023 250 browser details YourSeq 112 2737 2923 3000 87.2% chr12 + 16529475 16529659 185 browser details YourSeq 109 2749 2922 3000 80.0% chr2 + 179253505 179253676 172 browser details YourSeq 102 2745 2921 3000 87.7% chr16 - 97890583 97890758 176 browser details YourSeq 102 2792 2988 3000 78.7% chr7 + 136834710 136834893 184 browser details YourSeq 100 2745 2988 3000 89.2% chr10 - 120524101 120524344 244 browser details YourSeq 100 2838 3000 3000 80.9% chr8 + 48216950 48217116 167 browser details YourSeq 97 2756 3000 3000 87.9% chr10 - 79601958 79602201 244 browser details YourSeq 97 2793 2923 3000 83.9% chr10 - 40815235 40815352 118 browser details YourSeq 96 2838 3000 3000 79.8% chr2 - 164660271 164660437 167 browser details YourSeq 96 2838 3000 3000 79.8% chr16 - 93413022 93413188 167 browser details YourSeq 94 2796 2923 3000 86.8% chr19 + 25690143 25690270 128 browser details YourSeq 93 2806 2922 3000 96.1% chr9 - 70187120 70187477 358 browser details YourSeq 93 2838 2981 3000 82.7% chr5 - 110629255 110629402 148 browser details YourSeq 93 2787 2922 3000 84.6% chr10 - 63342380 63342527 148 browser details YourSeq 92 2838 3000 3000 78.6% chr10 - 68361806 68361972 167 browser details YourSeq 92 2784 2924 3000 84.2% chr5 + 130340196 130340332 137 browser details YourSeq 91 2739 3000 3000 76.4% chr16 + 30637651 30637911 261 browser details YourSeq 90 2788 2923 3000 86.2% chr15 + 84107636 84107765 130 Note: The 3000 bp section upstream of Exon 7 is BLAT searched against the genome. No significant similarity is found. BLAT Search Results (down) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 3000 1 3000 3000 100.0% chr3 + 28542350 28545349 3000 browser details YourSeq 207 206 553 3000 85.3% chr13 - 56512030 56512358 329 browser details YourSeq 202 206 532 3000 81.5% chr11 - 79479518 79479828 311 browser details YourSeq 194 206 523 3000 81.3% chr18 - 56895142 56895441 300 browser details YourSeq 190 209 541 3000 86.9% chr8 - 3374232 3374561 330 browser details YourSeq 182 214 526 3000 86.6% chr16 - 55666579 55666871 293 browser details YourSeq 181 207 537 3000 82.9% chr2 - 133050906 133051207 302 browser details YourSeq 180 212 483 3000 84.4% chr6 - 114066116 114066368 253 browser details YourSeq 179 206 526 3000 82.2% chr11 - 77262071 77262363 293 browser details YourSeq 176 222 498 3000 86.4% chr15 + 94878455 94878723 269 browser details YourSeq 175 206 498 3000 85.3% chr6 - 50331097 50331369 273 browser details YourSeq 175 206 537 3000 81.2% chr1 - 54033598 54033889 292 browser details YourSeq 175 206 554 3000 81.9% chr6 + 55986253 55986545 293 browser details YourSeq 174 210 488 3000 81.3% chr15 - 39224935 39225196 262 browser details YourSeq 174 208 511 3000 89.6% chr14 + 47875833 47876136 304 browser details YourSeq 173 206 483 3000 88.4% chr9 + 31948078 31948342 265 browser details YourSeq 173 212 498 3000 83.3% chr13 + 70490392 70490642 251 browser details YourSeq 172 214 487 3000 82.3% chr10 - 78061932 78062187 256 browser details YourSeq 170 206 472 3000 84.8% chr6 + 89435699 89435946 248 browser details YourSeq 169 189 493 3000 87.6% chr5 - 133878637 133878907 271 Note: The 3000 bp section downstream of Exon 7 is BLAT searched against the genome. No significant similarity is found. Page 4 of 8 https://www.alphaknockout.com Gene and protein information: Tnik TRAF2 and NCK interacting kinase [ Mus musculus (house mouse) ] Gene ID: 665113, updated on 10-Oct-2019 Gene summary Official Symbol Tnik provided by MGI Official Full Name TRAF2 and NCK interacting kinase provided by MGI Primary source MGI:MGI:1916264 See related Ensembl:ENSMUSG00000027692 Gene type protein coding RefSeq status VALIDATED Organism Mus musculus Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus Also known as AI451411; 1500031A17Rik; 4831440I19Rik; C530008O15Rik; C630040K21Rik Expression Broad expression in frontal lobe adult (RPKM 7.4), cortex adult (RPKM 5.7) and 18 other tissues See more Orthologs human all Genomic context Location: 3; 3 A3 See Tnik in Genome Data Viewer Exon count: 35 Annotation release Status Assembly Chr Location 108 current GRCm38.p6 (GCF_000001635.26) 3 NC_000069.6 (28261901..28670585) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 3 NC_000069.5 (28162136..28569507) Chromosome 3 - NC_000069.6 Page 5 of 8 https://www.alphaknockout.com Transcript information: This gene has 18 transcripts Gene: Tnik ENSMUSG00000027692 Description TRAF2 and NCK interacting kinase [Source:MGI Symbol;Acc:MGI:1916264] Gene Synonyms 1500031A17Rik, 4831440I19Rik, C530008O15Rik, C630040K21Rik Location Chromosome 3: 28,263,214-28,675,858 forward strand. GRCm38:CM000996.2 About this gene This gene has 18 transcripts (splice variants), 254 orthologues, 35 paralogues, is a member of 1 Ensembl protein family and is associated with 30 phenotypes. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Tnik- ENSMUST00000159236.8 12276 1323aa ENSMUSP00000124681.2 Protein coding CCDS50879 P83510 TSL:1 201 GENCODE basic APPRIS ALT1 Tnik- ENSMUST00000160307.8 4404 1360aa ENSMUSP00000125081.2 Protein coding CCDS50877 B2RQ80 TSL:1 205 GENCODE basic APPRIS P4 Tnik- ENSMUST00000159680.8 4380 1352aa ENSMUSP00000124876.2 Protein coding CCDS50878 B9EKN8 TSL:1 203 GENCODE basic APPRIS ALT1 Tnik- ENSMUST00000160518.7 3996 1331aa ENSMUSP00000124011.1 Protein coding - E9PUL9 TSL:5 206 GENCODE basic APPRIS ALT1 Tnik- ENSMUST00000162485.7 3918 1305aa ENSMUSP00000124387.1 Protein coding - E0CY98 TSL:5 214 GENCODE basic Tnik- ENSMUST00000162777.7 3894 1297aa ENSMUSP00000124726.1 Protein coding - E0CXD6 TSL:5 215 GENCODE basic Tnik- ENSMUST00000159308.7 3831 1276aa ENSMUSP00000125466.1 Protein coding - E0CZD7 TSL:5 202 GENCODE basic Tnik- ENSMUST00000161964.1 3807 1268aa ENSMUSP00000125411.1 Protein coding - E0CZF8 TSL:5 211 GENCODE basic Tnik- ENSMUST00000160934.7 7108 227aa ENSMUSP00000123859.1 Nonsense mediated - E0CYV5 TSL:1 207 decay Tnik- ENSMUST00000162037.8 4276 No - Retained intron - - TSL:1 212 protein Tnik- ENSMUST00000161214.7 2220 No - Retained intron - - TSL:1 208 protein Tnik- ENSMUST00000192205.1 1904 No - Retained intron - - TSL:NA 216 protein Tnik- ENSMUST00000193721.1 1815 No - Retained intron - - TSL:NA 217 protein Tnik- ENSMUST00000195094.1 1285 No - Retained intron - - TSL:NA 218 protein Tnik- ENSMUST00000159733.1 967 No - Retained intron - - TSL:1 204 protein Tnik- ENSMUST00000162225.1 826 No - Retained intron - - TSL:5 213 protein Page 6 of 8 https://www.alphaknockout.com Tnik- ENSMUST00000161234.7 658 No - Retained intron - - TSL:3 209 protein Tnik-
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