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Mouse Trip4 Conditional Knockout Project (CRISPR/Cas9)

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Mouse Trip4 Conditional Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Trip4 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Trip4 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Trip4 gene (NCBI Reference Sequence: NM_019797 ; Ensembl: ENSMUSG00000032386 ) is located on Mouse chromosome 9. 16 exons are identified, with the ATG start codon in exon 4 and the TGA stop codon in exon 16 (Transcript: ENSMUST00000119245). Exon 5 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Trip4 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-363H13 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: Exon 5 starts from about 5.85% of the coding region. The knockout of Exon 5 will result in frameshift of the gene. The size of intron 4 for 5'-loxP site insertion: 3867 bp, and the size of intron 5 for 3'-loxP site insertion: 1682 bp. The size of effective cKO region: ~670 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 5 6 16 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Trip4 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(7170bp) | A(28.77% 2063) | C(18.84% 1351) | T(32.61% 2338) | G(19.78% 1418) 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% chr9 - 65881311 65884310 3000 browser details YourSeq 239 2243 2595 3000 89.8% chr1 - 34487169 34487659 491 browser details YourSeq 237 2269 2595 3000 91.4% chr11 - 51660158 51660590 433 browser details YourSeq 234 2241 2587 3000 90.1% chr4 - 135887651 135888044 394 browser details YourSeq 234 2299 2624 3000 93.1% chr11 + 95295320 95295839 520 browser details YourSeq 221 2350 2666 3000 93.4% chr11 + 106616363 106616840 478 browser details YourSeq 220 2292 2602 3000 86.0% chr1 + 156694004 156694284 281 browser details YourSeq 215 2293 2602 3000 88.1% chr10 + 89852415 89852717 303 browser details YourSeq 206 2243 2605 3000 91.3% chrX + 153272083 153272465 383 browser details YourSeq 201 2301 2594 3000 90.3% chr5 + 105650516 105650808 293 browser details YourSeq 198 2299 2583 3000 92.8% chr4 - 98825510 98825860 351 browser details YourSeq 197 2329 2612 3000 88.7% chr3 + 95316795 95317075 281 browser details YourSeq 195 2329 2591 3000 90.8% chr13 + 24783668 24783942 275 browser details YourSeq 191 2329 2603 3000 92.1% chr9 - 22208984 22209602 619 browser details YourSeq 188 2329 2603 3000 88.3% chr8 - 105586963 105587229 267 browser details YourSeq 186 2256 2561 3000 89.2% chr7 + 92826774 92827101 328 browser details YourSeq 183 2334 2583 3000 93.5% chr5 - 110760079 110760678 600 browser details YourSeq 182 2454 2823 3000 87.7% chr4 + 133952130 133952775 646 browser details YourSeq 181 2211 2613 3000 85.3% chr13 + 45446988 45447234 247 browser details YourSeq 179 2449 2815 3000 82.8% chr2 - 157056716 157057048 333 Note: The 3000 bp section upstream of Exon 5 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% chr9 - 65877641 65880640 3000 browser details YourSeq 99 7 517 3000 81.1% chr12 - 16342942 16343340 399 browser details YourSeq 95 1198 1338 3000 86.3% chr10 + 61087766 61087918 153 browser details YourSeq 93 2 111 3000 92.8% chr10 - 76438029 76438160 132 browser details YourSeq 87 1171 1307 3000 80.2% chr16 - 4053970 4054098 129 browser details YourSeq 85 1 99 3000 94.8% chr12 + 31917137 32190127 272991 browser details YourSeq 81 2 109 3000 86.3% chr17 - 27151871 27151976 106 browser details YourSeq 81 1 109 3000 88.1% chr10 - 118038305 118038418 114 browser details YourSeq 81 1 109 3000 88.1% chr9 + 100569091 100569202 112 browser details YourSeq 80 1198 1307 3000 84.5% chr1 - 176596110 176596218 109 browser details YourSeq 79 1162 1312 3000 82.7% chr13 - 107537040 107537184 145 browser details YourSeq 78 1217 1318 3000 87.0% chr10 - 60181575 60181675 101 browser details YourSeq 77 1 108 3000 87.7% chr9 + 105162314 105162420 107 browser details YourSeq 75 471 574 3000 82.0% chr7 - 98761284 98761383 100 browser details YourSeq 75 1 109 3000 85.2% chrX + 145142870 145142977 108 browser details YourSeq 73 10 112 3000 85.6% chr5 - 76736085 76736186 102 browser details YourSeq 72 1 86 3000 91.9% chr4 - 59340655 59340740 86 browser details YourSeq 72 1 86 3000 91.9% chr14 - 64474041 64474126 86 browser details YourSeq 72 1 87 3000 91.9% chr6 + 97831872 97831961 90 browser details YourSeq 71 1 85 3000 89.3% chr2 - 117500906 117500989 84 Note: The 3000 bp section downstream of Exon 5 is BLAT searched against the genome. No significant similarity is found. Page 4 of 8 https://www.alphaknockout.com Gene and protein information: Trip4 thyroid hormone receptor interactor 4 [ Mus musculus (house mouse) ] Gene ID: 56404, updated on 14-Aug-2019 Gene summary Official Symbol Trip4 provided by MGI Official Full Name thyroid hormone receptor interactor 4 provided by MGI Primary source MGI:MGI:1928469 See related Ensembl:ENSMUSG00000032386 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 Asc1; ASC-1; BB191711; 4930558E03Rik Expression Ubiquitous expression in bladder adult (RPKM 5.1), testis adult (RPKM 4.6) and 28 other tissues See more Orthologs human all Genomic context Location: 9; 9 C See Trip4 in Genome Data Viewer Exon count: 17 Annotation release Status Assembly Chr Location 108 current GRCm38.p6 (GCF_000001635.26) 9 NC_000075.6 (65828926..65908875, complement) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 9 NC_000075.5 (65676733..65756601, complement) Chromosome 9 - NC_000075.6 Page 5 of 8 https://www.alphaknockout.com Transcript information: This gene has 10 transcripts Gene: Trip4 ENSMUSG00000032386 Description thyroid hormone receptor interactor 4 [Source:MGI Symbol;Acc:MGI:1928469] Gene Synonyms 4930558E03Rik, ASC-1 Location Chromosome 9: 65,828,930-65,908,794 reverse strand. GRCm38:CM001002.2 About this gene This gene has 10 transcripts (splice variants), 199 orthologues and is a member of 1 Ensembl protein family. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Trip4-210 ENSMUST00000179395.7 7055 539aa ENSMUSP00000137304.1 Protein coding CCDS52838 Q9QXN3 TSL:5 GENCODE basic Trip4-202 ENSMUST00000119245.7 4211 581aa ENSMUSP00000112385.1 Protein coding CCDS23298 Q9QXN3 TSL:1 GENCODE basic APPRIS P1 Trip4-203 ENSMUST00000122410.7 3915 539aa ENSMUSP00000112866.1 Protein coding CCDS52838 Q9QXN3 TSL:1 GENCODE basic Trip4-201 ENSMUST00000117083.1 1999 581aa ENSMUSP00000113949.1 Protein coding CCDS23298 Q9QXN3 TSL:1 GENCODE basic APPRIS P1 Trip4-207 ENSMUST00000134338.7 661 56aa ENSMUSP00000117648.1 Protein coding - D3Z3P3 CDS 3' incomplete TSL:5 Trip4-208 ENSMUST00000139346.1 576 No protein - Retained intron - - TSL:1 Trip4-205 ENSMUST00000132380.1 508 No protein - Retained intron - - TSL:3 Trip4-206 ENSMUST00000133747.7 1564 No protein - lncRNA - - TSL:1 Trip4-204 ENSMUST00000126517.7 907 No protein - lncRNA - - TSL:1 Trip4-209 ENSMUST00000143864.1 683 No protein - lncRNA - - TSL:2 Page 6 of 8 https://www.alphaknockout.com 99.86 kb Forward strand 65.82Mb 65.84Mb 65.86Mb 65.88Mb 65.90Mb Genes n-R5s85-201 >rRNA Pclaf-201 >protein coding Csnk1g1-206 >retained intron (Comprehensive set... Gm16073-201 >processed pseudogene Pclaf-202 >retained intron Csnk1g1-203 >retained intron Pclaf-203 >retained intron Csnk1g1-209 >protein coding Csnk1g1-216 >nonsense mediated decay Gm23248-201 >snRNA Csnk1g1-212 >protein coding Csnk1g1-201 >protein coding Csnk1g1-208 >protein coding Csnk1g1-214 >protein coding Csnk1g1-202 >protein coding Contigs < AC151906.3 Genes (Comprehensive set... < Zfp609-201protein codin<g Trip4-201protein coding < Trip4-206lncRNA < Trip4-210protein coding < Trip4-203protein coding < Trip4-204lncRNA < Trip4-202protein coding < Trip4-205retained intron < Trip4-207protein coding < Trip4-209lncRNA < Trip4-208retained intron Regulatory Build 65.82Mb 65.84Mb 65.86Mb 65.88Mb 65.90Mb Reverse strand 99.86 kb Regulation
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