| Primary Identifier | MGI:5904937 | Allele Type | Transgenic |
| Attribute String | Humanized sequence, Inserted expressed sequence | Gene | Tg(S100A8-PML/RARA*M883R*T886R)14Hdt |
| Strain of Origin | (C57BL/6 x CBA)F1 | Is Recombinase | false |
| Is Wild Type | false |
| molecularNote | A cDNA derived from the human PML/RARA (promyelocytic leukemia/retinoic acid receptor, alpha) fusion gene resulting from a T(15;17) chromosomal translocation typically associated with acute promyelocytic leukemia was modified to replace methionine and threonine at amino acid (aa) positions 883 and 886 of the RARA protein, respectively, with arginine (M883R and T886R), abrogating its binding to retinoid receptor alpha (RXRA). The modified cDNA has replaced the protein-coding region of the human S100A8 (also called MRP8) gene in the pUCMRP8d vector. The resultant construct contains the promoter, exon 1, intron 1 and the untranslated portion of exon 2 from S100A8 followed by the PML/RARA cDNA and the untranslated part of S100A8 exon 3. S100A8 is known to be expressed in early stages of the myeloid cell lineage and in peripheral neutrophils and monocytes, but not in tissue macrophages. The translocation, between breakpoint cluster region 1 (bcr1) in intron 6 of PML and a site in intron 2 of RARA, joins most of the 5' region of the PML gene to most of the 3' portion of the RARA gene. The resultant chimeric mRNA, which includes the alternatively spliced PML exon 5, contains a single open reading frame encoding a protein comprising 530 N-terminal amino acids (aa) of PML including the nuclear localization signal (nls) and all three sumoylation sites and 402 C-terminal aa from RARA including the DNA- and retinol-binding domains, but not the N-terminal A region, and containing the M883R and T886R aa replacements. All transgenic lines selected for study were shown by both western blot and immunofluorescence analysis to express the chimeric protein. |
