Irak3^tm1Flv
Targeted Allele Detail

Summary

• Symbol: Irak3^tm1Flv
• Name: interleukin-1 receptor-associated kinase 3; targeted mutation 1, Richard A Flavell
• MGI ID: MGI:2384197
• Synonyms: IRAK-M^-
• Gene: Irak3 Location: Chr10:119977553-120038035 bp, - strand Genetic Position: Chr10, 67.94 cM, cytoband D2
• Alliance: Irak3^tm1Flv page

Small size and reduced total bone mineral density in Irak3^tm1Flv/Irak3^tm1Flv mice

Show the 1 phenotype image(s) involving this allele.

Mutation origin

• Germline Transmission: Earliest citation of germline transmission: J:78189
• Parent Cell Line: W9.5/W95 (ES Cell)
• Strain of Origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺

Mutation description

• Allele Type: Targeted (Null/knockout)
• Mutations: Insertion, Intragenic deletion
• Mutation details: 1.2 kb of sequence were replaced with a floxed neo cassette. The deleted region contained 3 exons encoding two thirds of the kinase domain. While Western blot analysis of LPS-stimulated bone marrow macrophage extracts using a carboxy terminal antibody confirmed the absence of normal protein in homozygous mutant mice, truncated transcript was detected by Northern blot analysis using an amino terminal probe. Sequence analysis of RT-PCR products revealed an in frame stop codon generated by aberrant splicing of the endogenous gene and the neo transgene. (J:78189)

Phenotypes

Key:

hm	homozygous	ht	heterozygous	tg	involves transgenes	√	phenotype observed
cn	conditional genotype	cx	complex: > 1 genome feature	ot	other: hemizygous, indeterminate,...	N	normal phenotype

Genotype/
Background:

	Allelic Composition	Genetic Background	Cell Line(s)
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hm1  Disease Model	Irak3^tm1Flv/Irak3^tm1Flv	involves: 129S1/Sv * C57BL/6
hm2  Disease Model	Irak3^tm1Flv/Irak3^tm1Flv	NOD.129S1(B6)-Irak3^tm1Flv

Phenotypes:

Affected Systems	hm1	hm2
show or hide all annotated terms Sex:
endocrine/exocrine glands		√
insulitis		√
growth/size/body	√
decreased body size	√
hematopoietic system	√	√
abnormal T cell differentiation		√
increased neutrophil cell number	√
increased effector memory T-helper cell number		√
increased osteoclast cell number	√
abnormal T cell activation		√
abnormal osteoclast physiology	√
homeostasis/metabolism		√
impaired glucose tolerance		√
immune system	√	√
abnormal T cell activation		√
abnormal immune system morphology	√
abnormal T cell differentiation		√
increased neutrophil cell number	√
increased effector memory T-helper cell number		√
increased osteoclast cell number	√
abnormal Peyer's patch morphology	√
enlarged Peyer's patches	√
abnormal professional antigen presenting cell physiology		√
abnormal dendritic cell physiology		√
increased interleukin-12b secretion	√
increased interleukin-6 secretion	√
increased tumor necrosis factor secretion	√
increased susceptibility to autoimmune diabetes		√
increased anti-insulin autoantibody level		√
abnormal inflammatory response	√
insulitis		√
increased susceptibility to endotoxin shock	√
abnormal innate immunity	√
abnormal osteoclast physiology	√
limbs/digits/tail	√
decreased diameter of femur	√
skeleton	√
increased osteoclast cell number	√
abnormal osteoclast physiology	√
decreased diameter of femur	√
kyphosis	√
abnormal compact bone morphology	√
decreased compact bone thickness	√
increased osteoblast cell number	√
abnormal trabecular bone morphology	√
decreased trabecular bone volume	√

View phenotypes and curated references for all genotypes (concatenated display).

Disease models

Key:

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disease model

expected model not found

Models:

Human Diseases	hm1	hm2
osteoporosis IDs osteoporosis       DOID:11476 EFO:0003882 ICD10CM:M81.0 ICD9CM:733.0 ICD9CM:733.00 MESH:D010024 NCI:C3298 OMIM:166710 UMLS_CUI:C0029456 Close	√
type 1 diabetes mellitus IDs type 1 diabetes mellitus       DOID:9744 ICD10CM:E10 KEGG:04940 MESH:D003922 NCI:C2986 OMIM:222100 UMLS_CUI:C0011854 Close		√

Expression

In Structures Affected by this Mutation:

6 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 2 strains available Cell Lines: 0 lines available
• Carrying any Irak3 Mutation: 104 strains or lines available

References

• Original: J:78189 Kobayashi K, et al., IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002 Jul 26;110(2):191-202
• All: 31 reference(s)