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Mtf1Thyls-MSM
QTL Variant Detail
Nomenclature
QTL variant: Mtf1Thyls-MSM
Name: metal response element binding transcription factor 1; MSM
MGI ID: MGI:2155609
QTL: Mtf1  Location: Chr4:124802549-124849800 bp, + strand  Genetic Position: Chr4, 57.91 cM, cytoband D1
Variant
origin
Strain of Specimen:  multiple strains
Variant
description
Allele Type:    QTL
Mutation:    Single point mutation
 
Mutation detailsA T to C difference in the coding sequence in MSM and AKR strains alters the amino acid at position 424 from a serine to a proline. This allele confers resistance to gamma-irradiation and MNU-induced thymic lymphomas compared to MSM. (J:95547)
Inheritance:    Recessive
Phenotypes
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View phenotypes and curated references for all genotypes (concatenated display).
Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:105074

Susceptibility to radiation induced acute myeloid leukemia (AML) was mapped by genomic microsatellite analysis of 9 inbred strains. AML susceptible strains, such as CBA/H and CBA/Ca, exhibit a high frequency of chromosome 2 deletions in bone marrow cellsfollowing whole body irradiation whereas resistant strains, such as C57BL/6J, do not. Loci were detected on mouse Chromosomes 3, 4, 8, and 18. A limited (CBA/Ca x C57BL/6J)F1 x C57BL/6J backcross was used to confirm the QTLs.

Raml1 (radiation induced acute myeloid leukemia 1) mapped to mouse Chromosome 18 with strongest linkage at D18Mit146 (4 cM) and D18Mit229 (4 cM). C57BL/6J-derived alleles at Raml1 confer sensitivity to radiation induced chromosome 2 deletions and, by association, AML. Loss of heterozygosity was not observed in this region. Potential candidate genes in this region are Rbbp8, Riok3 (3 cM), 3110002H16Rik (Mic1), Npc1 (4 cM), Ankrd29, and Lama3 (3 cM). Rbbp8 was identified as a strong candidate as this gene is upregulated in response toX-irradiation inCBA mice. Raml1 is syntenic to human 18q11, a region implicated in 322 cases of cancer.

Raml2 (radiation induced acute myeloid leukemia 2) mapped to 61.8 cM on mouse Chromosome 3 near D3Mit319. This locus is syntenic to human Chromosome 4q25. Bomb1 (61.8cM) is a previously identified bone marrow lymphoma QTL co-localizing with Raml2.

Raml3 (radiation induced acute myeloid leukemia 3) mapped to 55.2 cM on mouse Chromosome 4 near D4Mit248. This locus is syntenic to human Chromosome 1p34. Mycl1 (previously Lmyc; 55 cM) is a potential candidate gene for Raml3. Previously identified tumor susceptibility QTLs Thyls (55 cM) and Skts7 (56 cM) are found near Raml3.

Raml4 (radiation induced acute myeloid leukemia 4) mapped to 33 cM on mouse Chromosome 8 near D8Mit178. This locus is syntenic to human Chromosome 19p13. Rab3a (32.6 cM) and Rab8a (33 cM) are potential candidate genes mapping near Raml4.

Raml5 (radiation induced acute myeloid leukemia 5) mapped to mouse Chromosome 13 near D13Mit23. Nsd1, Mxd3 (formerly Mad3; 32 cM), and Msx2 (formerly Hox8; 32 cM) are potential candidate genes for Raml5.

References
Original:  J:71358 Saito Y, et al., Genetic loci controlling susceptibility to gamma-ray-induced thymic lymphoma. Oncogene. 2001 Aug 23;20(37):5243-7
All:  4 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
08/04/2020
MGI 6.15
The Jackson Laboratory