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Spi1tm1.3Dgt
Targeted Allele Detail
Summary
Symbol: Spi1tm1.3Dgt
Name: Spi-1 proto-oncogene; targeted mutation 1.3, Daniel G Tenen
MGI ID: MGI:3619530
Synonyms: PU.1 knockdown, UREdelta, UREdelta (neo-)
Gene: Spi1  Location: Chr2:90912750-90946104 bp, + strand  Genetic Position: Chr2, 50.44 cM, cytoband E3
Alliance: Spi1tm1.3Dgt page
Mutation
origin
Germline Transmission:  Earliest citation of germline transmission: J:106040
Parent Cell Line:  R1 (ES Cell)
Strain of Origin:  (129X1/SvJ x 129S1/Sv)F1-Kitl+
Mutation
description
Allele Type:    Targeted (Null/knockout)
Mutations:    Insertion, Intragenic deletion
 
Mutation detailsThis allele was generated from Sfpi1tm1Dgt by sequential deletion of the loxP-flanked 3.4-kb upstream regulatory element (URE), located 14 kb upstream from the endogenous gene, and of the FRT-flanked PGK-Neo cassette residing immediately upstream of the URE, achieved by crossing mice bearing the Sfpi1 mutations with animals ubiquitously expressing Cre and FLP recombinase, respectively. Thus it lacks both the normal URE and the introduced PGK-neo cassette, with single loxP and FRT sites marking their former locations. Expression of the gene in bone marrow and purified hematopoietic stem cells (HSCs) of homozygous mutant mice is reduced to ~80% of wild-type levels. (J:90331, J:106040, J:106789)
Phenotypes
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View phenotypes and curated references for all genotypes (concatenated display).
Disease models
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Expression
In Structures Affected by this Mutation: 4 anatomical structure(s)
Find Mice (IMSR)
Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
Carrying this Mutation:  Mouse Strains: 1 strain available      Cell Lines: 0 lines available
Carrying any Spi1 Mutation:  27 strains or lines available
Notes
Although expression of PU.1/SFPI1 in hematopoietic stem cells, myeloid progenitor cells and granulocytes is similar in mice homozygous for this mutation and for Sfpi1tm1.1Dgt ("UREdeltaneo"), which retains the PGK-neo cassette, mice with the present mutation develop acute myelocytic leukemia (AML) with a lower penetrance (29% vs. 97%) and a longer latency (6-12 months vs. 3-8 months) than do those with Sfpi1tm1.1Dgt. Mice with the present mutation often die of T cell lymphoma before the time of onset of AML. (J:106789;J:90331) The phenotypic difference may be due to genetic background differences, as Sfpi1tm1.1Dgt was analyzed on a ~50% BALB/c and the present mutation on a greater than 50% 129/Sv background.
References
Original:  J:106040 Rosenbauer F, et al., Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat Genet. 2006 Jan;38(1):27-37
All:  12 reference(s)

Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/19/2024
MGI 6.23
The Jackson Laboratory