Spi1^tm1.3Dgt
Targeted Allele Detail

Summary

• Symbol: Spi1^tm1.3Dgt
• 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: Spi1^tm1.3Dgt 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 details: This allele was generated from Sfpi1^tm1Dgt 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)

Disease models

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: 28 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 Sfpi1^tm1.1Dgt ("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 Sfpi1^tm1.1Dgt. 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 Sfpi1^tm1.1Dgt 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: 13 reference(s)