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Mouse Kmo Knockout Project (CRISPR/Cas9)

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Mouse Kmo Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse Kmo Knockout Project (CRISPR/Cas9) Objective: To create a Kmo knockout Mouse model (C57BL/6N) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Kmo gene (NCBI Reference Sequence: NM_133809 ; Ensembl: ENSMUSG00000039783 ) is located on Mouse chromosome 1. 15 exons are identified, with the ATG start codon in exon 1 and the TAG stop codon in exon 15 (Transcript: ENSMUST00000040250). Exon 2~6 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a knock-out allele lack kynurenine 3-monooxygenase activity and altered levels of several tryptophan metabolites. Mice homozygous for another null allele exhibit increased LPS-induced depressive behaviors and altered kynurenine metabolism. Exon 2 starts from about 3.83% of the coding region. Exon 2~6 covers 27.49% of the coding region. The size of effective KO region: ~9692 bp. The KO region does not have any other known gene. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 4 5 6 15 Legends Exon of mouse Kmo Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 2 is aligned with itself to determine if there are tandem repeats. Tandem repeats are found in the dot plot matrix. The gRNA site is selected outside of these tandem repeats. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 1951 bp section downstream of Exon 6 is aligned with itself to determine if there are tandem repeats. Tandem repeats are found in the dot plot matrix. The gRNA site is selected outside of these tandem repeats. Page 3 of 9 https://www.alphaknockout.com Overview of the GC Content Distribution (up) Window size: 300 bp Sequence 12 Summary: Full Length(2000bp) | A(23.4% 468) | C(26.9% 538) | T(32.75% 655) | G(16.95% 339) Note: The 2000 bp section upstream of Exon 2 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. Overview of the GC Content Distribution (down) Window size: 300 bp Sequence 12 Summary: Full Length(1951bp) | A(21.48% 419) | C(23.27% 454) | T(36.55% 713) | G(18.71% 365) Note: The 1951 bp section downstream of Exon 6 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 4 of 9 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 2000 1 2000 2000 100.0% chr1 + 175635510 175637509 2000 browser details YourSeq 122 262 385 2000 99.2% chr8 + 116343108 116343231 124 browser details YourSeq 121 260 380 2000 100.0% chr5 + 131367403 131367523 121 browser details YourSeq 119 253 387 2000 94.9% chr2 - 9904833 9904969 137 browser details YourSeq 115 251 365 2000 100.0% chr2 + 20029443 20029557 115 browser details YourSeq 107 253 359 2000 100.0% chr6 - 128525559 128525665 107 browser details YourSeq 106 275 380 2000 100.0% chr17 + 45240944 45241049 106 browser details YourSeq 102 278 381 2000 99.1% chr6 + 50956161 50956264 104 browser details YourSeq 102 271 374 2000 99.1% chr6 + 50956161 50956264 104 browser details YourSeq 100 252 429 2000 88.2% chr8 - 103628019 103628188 170 browser details YourSeq 99 252 385 2000 84.0% chr11 - 9949454 9949559 106 browser details YourSeq 97 267 385 2000 90.9% chr9 + 91348282 91348402 121 browser details YourSeq 96 289 384 2000 100.0% chr5 + 83089806 83089901 96 browser details YourSeq 92 273 368 2000 98.0% chr16 - 87579225 87579320 96 browser details YourSeq 92 266 361 2000 98.0% chr16 - 87579225 87579320 96 browser details YourSeq 92 259 354 2000 98.0% chr16 - 87579225 87579320 96 browser details YourSeq 91 293 383 2000 100.0% chr2 + 172051430 172051520 91 browser details YourSeq 84 301 384 2000 100.0% chr13 + 98480695 98480778 84 browser details YourSeq 79 297 385 2000 88.1% chr11 - 9949460 9949543 84 browser details YourSeq 73 270 366 2000 95.2% chr6 - 71764916 71765031 116 Note: The 2000 bp section upstream of Exon 2 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 1951 1 1951 1951 100.0% chr1 + 175647202 175649152 1951 browser details YourSeq 169 967 1178 1951 92.5% chr16 - 87448412 87448729 318 browser details YourSeq 167 959 1186 1951 87.5% chr17 + 56646343 56646552 210 browser details YourSeq 164 956 1185 1951 88.2% chr16 + 81784051 81784266 216 browser details YourSeq 161 952 1186 1951 88.5% chr9 - 102828404 102828626 223 browser details YourSeq 159 982 1181 1951 90.4% chrX + 158493226 158493430 205 browser details YourSeq 159 947 1186 1951 87.2% chr3 + 95611988 95612167 180 browser details YourSeq 157 949 1181 1951 84.9% chr1 - 17390299 17390495 197 browser details YourSeq 157 993 1186 1951 93.9% chr17 + 27534240 27534663 424 browser details YourSeq 155 929 1185 1951 84.0% chr1 + 86485865 86486052 188 browser details YourSeq 151 992 1185 1951 91.1% chr1 - 110857930 110858125 196 browser details YourSeq 150 947 1182 1951 92.3% chr7 - 140086808 140087184 377 browser details YourSeq 149 969 1178 1951 85.2% chr2 - 100863645 100863827 183 browser details YourSeq 149 952 1186 1951 85.0% chr15 + 84646918 84647113 196 browser details YourSeq 149 985 1186 1951 84.5% chr1 + 8896956 8897151 196 browser details YourSeq 148 1004 1189 1951 87.4% chr8 - 113457130 113457311 182 browser details YourSeq 148 1009 1182 1951 93.1% chr18 - 89564935 89565119 185 browser details YourSeq 148 949 1182 1951 85.4% chr16 - 10815766 10815962 197 browser details YourSeq 148 947 1183 1951 86.2% chr11 - 86255154 86255321 168 browser details YourSeq 148 989 1187 1951 86.8% chr10 - 84012018 84012192 175 Note: The 1951 bp section downstream of Exon 6 is BLAT searched against the genome. No significant similarity is found. Page 5 of 9 https://www.alphaknockout.com Gene and protein information: Kmo kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) [ Mus musculus (house mouse) ] Gene ID: 98256, updated on 17-Aug-2019 Gene summary Official Symbol Kmo provided by MGI Official Full Name kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) provided by MGI Primary source MGI:MGI:2138151 See related Ensembl:ENSMUSG00000039783 Gene type protein coding RefSeq status PROVISIONAL Organism Mus musculus Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus Also known as AI046660 Expression Biased expression in liver adult (RPKM 28.0), kidney adult (RPKM 18.4) and 6 other tissuesS ee more Orthologs human all Genomic context Location: 1; 1 H3 See Kmo in Genome Data Viewer Exon count: 15 Annotation release Status Assembly Chr Location 108 current GRCm38.p6 (GCF_000001635.26) 1 NC_000067.6 (175632193..175660853) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 1 NC_000067.5 (177562324..177590984) Chromosome 1 - NC_000067.6 Page 6 of 9 https://www.alphaknockout.com Transcript information: This gene has 6 transcripts Gene: Kmo ENSMUSG00000039783 Description kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) [Source:MGI Symbol;Acc:MGI:2138151] Location Chromosome 1: 175,620,381-175,662,116 forward strand. GRCm38:CM000994.2 About this gene This gene has 6 transcripts (splice variants), 205 orthologues, 1 paralogue, is a member of 1 Ensembl protein family and is associated with 6 phenotypes. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags Kmo- ENSMUST00000040250.14 2695 479aa ENSMUSP00000038914.8 Protein coding CCDS15548 Q91WN4 TSL:1 201 GENCODE basic APPRIS P2 Kmo- ENSMUST00000097458.3 3672 445aa ENSMUSP00000095067.3 Protein coding - Q91WN4 TSL:5 202 GENCODE basic APPRIS ALT2 Kmo- ENSMUST00000140474.7 1528 255aa ENSMUSP00000122943.1 Nonsense mediated - Q3V0K6 TSL:1 204 decay Kmo- ENSMUST00000142223.7 1600 No - Retained intron - - TSL:1 205 protein Kmo- ENSMUST00000150646.1 459 No - lncRNA - - TSL:3 206 protein Kmo- ENSMUST00000137174.1 374 No - lncRNA - - TSL:5 203 protein Page 7 of 9 https://www.alphaknockout.com 61.74 kb Forward strand 175.62Mb 175.63Mb 175.64Mb 175.65Mb 175.66Mb 175.67Mb Genes (Comprehensive set... Kmo-204 >nonsense mediated decay Kmo-201 >protein coding Kmo-205 >retained intron Kmo-206 >lncRNA Kmo-202 >protein coding Kmo-203 >lncRNA Contigs AC124366.4 > Genes < Fh1-201protein coding < Opn3-201protein coding (Comprehensive set... < Fh1-204nonsense mediated decay Regulatory Build 175.62Mb 175.63Mb 175.64Mb 175.65Mb 175.66Mb 175.67Mb Reverse strand 61.74 kb Regulation Legend CTCF Enhancer Open Chromatin Promoter Promoter Flank Transcription Factor Binding Site Gene Legend Protein Coding merged Ensembl/Havana Ensembl protein coding Non-Protein Coding RNA gene processed transcript Page 8 of 9 https://www.alphaknockout.com Transcript: ENSMUST00000040250 28.86 kb Forward strand Kmo-201 >protein coding ENSMUSP00000038... Transmembrane heli... Low complexity (Seg) Superfamily FAD/NAD(P)-binding domain superfamily Prints PR00420 Pfam FAD-binding domain PANTHER PTHR46028 PTHR46028:SF2 HAMAP Kynurenine 3-monooxygenase Gene3D FAD/NAD(P)-binding domain superfamily All sequence SNPs/i... Sequence variants (dbSNP and all other sources) Variant Legend missense variant splice region variant synonymous variant Scale bar 0 40 80 120 160 200 240 280 320 360 400 479 We wish to acknowledge the following valuable scientific information resources: Ensembl, MGI, NCBI, UCSC.
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