Phenotypes associated with this allele

• Allele Symbol: Map3k8^M1Btlr
• Allele Name: mutation 1, Bruce Beutler
• Allele ID: MGI:3795881
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Map3k8^M1Btlr/Map3k8^M1Btlr	C57BL/6J-Map3k8^M1Btlr	MGI:3817426
ht2	Map3k8^M1Btlr/Map3k8^+	C57BL/6J-Map3k8^M1Btlr	MGI:3817421

Genotype
MGI:3817426

hm1

• Allelic Composition: Map3k8^M1Btlr/Map3k8^M1Btlr
• Genetic Background: C57BL/6J-Map3k8^M1Btlr

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

prenatal lethality, incomplete penetrance ( J:140986 )

• very few mice homozygous for this mutation are born; the developmental stage at which death occurs has not been determined

• surviving homozygous mutants exhibit no overt phenotypic defects, are viable, and can breed

immune system

impaired natural killer cell mediated cytotoxicity ( J:140986 )

• homozygous mutant mice have impaired natural killer (NK) cell cyotoxicity in vivo as measured by reduced clearance of MHC class 1-deficient cells

decreased interferon-alpha secretion ( J:140986 )

• peritoneal macrophages from homozygous mutant mice fail to produce interferon alpha/beta (IFN-alpha/beta) in response to signaling via TLR7 or TLR9

• mutant macrophages exhibit a normal interferon response to LPS (via TLR4) and to poly I:C (via TLR3)

decreased interferon-beta secretion ( J:140986 )

• peritoneal macrophages from homozygous mutant mice fail to produce interferon alpha/beta (IFN-alpha/beta) in response to signaling via TLR7 or TLR9

• mutant macrophages exhibit a normal interferon response to LPS (via TLR4) and to poly I:C (via TLR3)

decreased interleukin-1 beta secretion ( J:140986 )

• the interleukin 1 beta (IL-1beta) response to LPS signaling via TLR4 is abolished in mutant macrophages

increased interleukin-12b secretion ( J:140986 )

• production of interleukin- (IL-) 12/p40 by mutant macrophages is elevated in response to signaling via TLR7 and vai TLR9

decreased interleukin-6 secretion ( J:140986 )

• mutant macrophages have an impaired interleukin- (IL-) 6 response to PGN (via TLR2/6), to Pam3CSK4 (via TLR1/2), and to resiquimod (via TLR7)

decreased tumor necrosis factor secretion ( J:140986 )

• peritoneal macrophages from homozygous mutants fail to produce TNF-alpha in response to viral infection

• peritoneal macrophages from homozygous mutants mice do not secrete tumor necrosis factor (TNF) -alpha in response to the TLR2/6 ligands MALP2 (macrophage-activating lipopeptide 2) and peptidoglycan or to CpG DNA, a TLR9 ligand

• although it is not secreted, normal intracellular levels of TNF-alpha are observed in MALP2-, peptidoglycan-, and CpG-stimulated mutant macrophages

• secretion of TNF-alpha in response to the TLR4 ligand, lipopolysaccharide (LPS), and to resiquimod, a ssRNA analog that signals via TLR7, is greatly reduced

• homozygous mutant macrophages exhibit a partially attenuated TNF-alpha response to the TLR1/2 ligand Pam3CSK4, a triacyl lipopeptide; and to the TLR3 ligand poly I:C, a double-stranded DNA mimetic

abnormal response to infection ( J:140986 )

• peritoneal macrophages from homozygous mutants fail to produce TNF-alpha in response to viral infection

• homozygous mutant macrophages show normal resistance to mouse cytomegalovirus (MCMV) and normal restriction of GFP expression when infected by a non-replicating recombinant Adenovirus 5 vector

hematopoietic system

impaired natural killer cell mediated cytotoxicity ( J:140986 )

• homozygous mutant mice have impaired natural killer (NK) cell cyotoxicity in vivo as measured by reduced clearance of MHC class 1-deficient cells

Genotype
MGI:3817421

ht2

• Allelic Composition: Map3k8^M1Btlr/Map3k8⁺
• Genetic Background: C57BL/6J-Map3k8^M1Btlr

mortality/aging

prenatal lethality, incomplete penetrance ( J:140986 )

• only ~25% of the expected number of heterozygous mutant mice are born; the developmental stage at which death occurs has not been determined

• surviving heterozygotes exhibit no overt phenotypic defects, are viable, and can breed

immune system

abnormal tumor necrosis factor secretion ( J:140986 )

• heterozygous macrophages secrete somewhat diminished levels of TNF-alpha in response to lower doses of the TLR1/2 ligand Pam3SK4, but slightly elevated levels in response to higher doses

decreased tumor necrosis factor secretion ( J:140986 )

• peritoneal macrophages from mice heterozygous for this mutation exhibit impairment in TNF-alpha secretion in response to MALP2 and PGN signaling via TLR1/2, CpG-DNA signaling via TLR9, and LPS signaling via TLR4

• resiquimod signaling via TLR7 stimulates statistically normal TNF-alpha secretion by heterozygous mutant macrophages