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Mouse A2ml1 Knockout Project (CRISPR/Cas9)

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Mouse A2ml1 Knockout Project (CRISPR/Cas9) https://www.alphaknockout.com Mouse A2ml1 Knockout Project (CRISPR/Cas9) Objective: To create a A2ml1 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The A2ml1 gene (NCBI Reference Sequence: NM_001001179.3 ; Ensembl: ENSMUSG00000047228 ) is located on Mouse chromosome 6. 36 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 35 (Transcript: ENSMUST00000060574). Exon 4~11 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: Exon 4 starts from about 9.32% of the coding region. Exon 4~11 covers 18.93% of the coding region. The size of effective KO region: ~8855 bp. The KO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 4 5 6 7 8 9 10 11 36 Legends Exon of mouse A2ml1 Knockout region Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 1536 bp section upstream of Exon 4 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 Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 1002 bp section downstream of Exon 11 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. Page 3 of 8 https://www.alphaknockout.com Overview of the GC Content Distribution (up) Window size: 300 bp Sequence 12 Summary: Full Length(1536bp) | A(32.16% 494) | C(18.03% 277) | T(31.51% 484) | G(18.29% 281) Note: The 1536 bp section upstream of Exon 4 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(1002bp) | A(29.24% 293) | C(24.05% 241) | T(24.35% 244) | G(22.36% 224) Note: The 1002 bp section downstream of Exon 11 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 8 https://www.alphaknockout.com BLAT Search Results (up) QUERY SCORE START END QSIZE IDENTITY CHROM STRAND START END SPAN ----------------------------------------------------------------------------------------------- browser details YourSeq 1536 1 1536 1536 100.0% chr6 - 128578787 128580322 1536 browser details YourSeq 41 687 945 1536 64.5% chr1 + 24513533 24513682 150 browser details YourSeq 31 1020 1056 1536 94.2% chr1 - 20173982 20174028 47 browser details YourSeq 28 632 662 1536 96.7% chr2 + 132663176 132663226 51 browser details YourSeq 27 996 1023 1536 100.0% chr15 + 3336376 3336410 35 browser details YourSeq 26 942 975 1536 96.5% chr2 + 118576307 118576341 35 browser details YourSeq 24 712 737 1536 96.2% chr1 - 34250151 34250176 26 browser details YourSeq 23 373 395 1536 100.0% chr8 - 73717190 73717212 23 browser details YourSeq 23 5 27 1536 100.0% chr4 + 67298470 67298492 23 browser details YourSeq 23 633 656 1536 100.0% chr1 + 42161372 42161396 25 browser details YourSeq 22 373 394 1536 100.0% chrY - 56042061 56042082 22 browser details YourSeq 22 629 650 1536 100.0% chr2 - 75833356 75833377 22 browser details YourSeq 22 630 651 1536 100.0% chrX + 69516995 69517016 22 browser details YourSeq 22 630 651 1536 100.0% chr9 + 51264205 51264226 22 browser details YourSeq 22 3 27 1536 96.0% chr18 + 74018751 74018776 26 browser details YourSeq 21 996 1016 1536 100.0% chr2 - 67149456 67149476 21 browser details YourSeq 21 648 668 1536 100.0% chr10 - 12429721 12429741 21 browser details YourSeq 21 630 650 1536 100.0% chr10 + 87870301 87870321 21 browser details YourSeq 20 631 650 1536 100.0% chr1 - 21782858 21782877 20 browser details YourSeq 20 649 670 1536 95.5% chr1 + 23546240 23546261 22 Note: The 1536 bp section upstream of Exon 4 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 1002 1 1002 1002 100.0% chr6 - 128568930 128569931 1002 browser details YourSeq 147 166 323 1002 94.2% chr2 + 70736928 70737080 153 browser details YourSeq 147 94 320 1002 95.1% chr10 + 76088780 76089072 293 browser details YourSeq 144 93 315 1002 94.5% chr1 + 182221236 182221751 516 browser details YourSeq 141 166 320 1002 93.5% chr1 + 74205511 74205662 152 browser details YourSeq 140 160 315 1002 95.5% chrX - 169481561 169481728 168 browser details YourSeq 140 166 315 1002 97.4% chr3 + 40967054 40967207 154 browser details YourSeq 140 166 315 1002 97.4% chr15 + 82253905 82254058 154 browser details YourSeq 139 92 317 1002 87.2% chr4 - 136037481 136037651 171 browser details YourSeq 139 166 315 1002 94.6% chr1 + 176798401 176798548 148 browser details YourSeq 138 166 422 1002 93.8% chr17 - 78529722 78530085 364 browser details YourSeq 138 166 315 1002 97.4% chr5 + 117496161 117496316 156 browser details YourSeq 137 167 317 1002 94.7% chr12 - 3919895 3920044 150 browser details YourSeq 137 166 313 1002 96.7% chr1 - 134519196 134519344 149 browser details YourSeq 137 166 317 1002 93.4% chr1 - 114982618 114982767 150 browser details YourSeq 137 166 309 1002 98.0% chr1 - 85987007 85987151 145 browser details YourSeq 137 172 320 1002 96.7% chr13 + 40977364 40977516 153 browser details YourSeq 136 172 315 1002 98.0% chr2 - 74167561 74167713 153 browser details YourSeq 136 166 309 1002 95.9% chr17 - 42931594 42931736 143 browser details YourSeq 136 170 315 1002 94.5% chr10 - 7188379 7188522 144 Note: The 1002 bp section downstream of Exon 11 is BLAT searched against the genome. No significant similarity is found. Page 5 of 8 https://www.alphaknockout.com Gene and protein information: A2ml1 alpha-2-macroglobulin like 1 [ Mus musculus (house mouse) ] Gene ID: 232400, updated on 26-Jun-2020 Gene summary Official Symbol A2ml1 provided by MGI Official Full Name alpha-2-macroglobulin like 1 provided by MGI Primary source MGI:MGI:3039594 See related Ensembl:ENSMUSG00000047228 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 Ovos; Ovos2 Expression Biased expression in ovary adult (RPKM 19.2), liver E18 (RPKM 5.0) and 1 other tissue See more Genomic context Location: 6; 6 F3 See A2ml1 in Genome Data Viewer Exon count: 36 Annotation release Status Assembly Chr Location 108.20200622 current GRCm38.p6 (GCF_000001635.26) 6 NC_000072.6 (128539822..128581606, complement) Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 6 NC_000072.5 (128489840..128531624, complement) Chromosome 6 - NC_000072.6 Page 6 of 8 https://www.alphaknockout.com Transcript information: This gene has 5 transcripts Gene: A2ml1 ENSMUSG00000047228 Description alpha-2-macroglobulin like 1 [Source:MGI Symbol;Acc:MGI:3039594] Gene Synonyms BC048546, Ovos2 Location Chromosome 6: 128,539,821-128,581,608 reverse strand. GRCm38:CM000999.2 About this gene This gene has 5 transcripts (splice variants), 744 orthologues, 10 paralogues and is a member of 1 Ensembl protein family. Transcripts Name Transcript ID bp Protein Translation ID Biotype CCDS UniProt Flags A2ml1-201 ENSMUST00000060574.8 4695 1456aa ENSMUSP00000059426.7 Protein coding CCDS39651 Q3UU35 TSL:1 GENCODE basic APPRIS P1 A2ml1-202 ENSMUST00000203129.1 2563 No protein - Retained intron - - TSL:NA A2ml1-204 ENSMUST00000203889.1 748 No protein - Retained intron - - TSL:2 A2ml1-203 ENSMUST00000203291.1 700 No protein - Retained intron - - TSL:1 A2ml1-205 ENSMUST00000205167.1 670 No protein - Retained intron - - TSL:3 61.79 kb Forward strand Contigs AC123060.4 > Genes (Comprehensive set... < Gm8724-201processed pseudogene < A2ml1-205retained intron < A2ml1-204retained intron < A2ml1-202retained intron < Gm44009-201lincRNA < A2ml1-203retained intron < A2ml1-201protein coding Regulatory Build Reverse strand 61.79 kb Regulation Legend CTCF Enhancer Open Chromatin Promoter Promoter Flank Gene Legend Protein Coding merged Ensembl/Havana Non-Protein Coding pseudogene processed transcript RNA gene Page 7 of 8 https://www.alphaknockout.com Transcript: ENSMUST00000060574 < A2ml1-201protein coding Reverse strand 41.78 kb ENSMUSP00000059... Low complexity (Seg) Cleavage site (Sign... Superfamily Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid Immunoglobulin E-set Alpha-macroglobulin, receptor-binding domain superfamily SMART Alpha-2-macroglobulin, bait region domain Alpha-macroglobulin, receptor-binding Alpha-2-macroglobulin Pfam Macroglobulin domain Alpha-2-macroglobulin Alpha-macroglobulin, receptor-binding Alpha-2-macroglobulin, bait region domain Alpha-macroglobulin-like, TED domain Macroglobulin domain MG4 Macroglobulin domain MG3 PROSITE patterns Alpha-2-macroglobulin, conserved site PANTHER PTHR11412 PTHR11412:SF152 Gene3D 2.60.40.1930 2.20.130.20 1.50.10.20 Alpha-macroglobulin, receptor-binding domain superfamily 2.60.40.1940 2.60.120.1540 Immunoglobulin-like fold CDD Alpha-2-macroglobulin, TED domain All sequence SNPs/i... Sequence variants (dbSNP and all other sources) Variant Legend missense variant splice region variant synonymous variant Scale bar 0 200 400 600 800 1000 1200 1456 We wish to acknowledge the following valuable scientific information resources: Ensembl, MGI, NCBI, UCSC. Page 8 of 8.
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