Phenotypes Associated with This Genotype

Genotype
MGI:4847651

• Allelic Composition: Tbk1^tm1.1Lex/Tbk1^tm1.1Lex
• Genetic Background: involves: 129S4/SvJae * 129S5/SvEvBrd

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

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:166476 )

• mice exhibit increased susceptibility to LPS-induced lethality compared with similarly treated wild-type mice

prenatal lethality, incomplete penetrance ( J:166476 )

• Background Sensitivity: fewer than expected mice are born

immune system

increased spleen weight ( J:166476 )

• slight

decreased NK T cell number ( J:166476 )

• mice exhibit reduced CD3+ and CD3+CD8+ T cells compared with wild-type mice

increased NK T cell number ( J:166476 )

• mice exhibit a slight increase in CD3+CD4+ T cells compared with wild-type mice

increased monocyte cell number ( J:166476 )

increased IgA level ( J:166476 )

• 1.5- to 3-fold

abnormal cytokine level ( J:166476 )

increased circulating interleukin-1 beta level ( J:166476 )

• in LPS-treated mice

increased circulating interleukin-10 level ( J:166476 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:166476 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:166476 )

• in LPS-treated mice

lymphoid hyperplasia ( J:166476 )

• in the spleen

abnormal cytokine secretion ( J:166476 )

decreased interferon-beta secretion ( J:166476 )

• in bone marrow-derived macrophages stimulated with LPS or pIpC

increased interleukin-6 secretion ( J:166476 )

• 2-fold in bone marrow-derived macrophages stimulated with LPS

• however, IL6 production up to 8 hours after LPS stimulation is normal in two subsequent experiments

increased tumor necrosis factor secretion ( J:166476 )

• 2-fold in bone marrow-derived macrophages stimulated with LPS

• however, TNF production up to 8 hours after LPS stimulation is normal in two subsequent experiments

abnormal inflammatory response ( J:166476 )

• mice exhibit increased infiltration of mononuclear and/or granulomatous cells in multiple organs and tissues including lungs, liver, kidney, skin, salivary gland, Hardrian gland, epididymides, and joint synovium compared with wild-type mice

increased susceptibility to endotoxin shock ( J:166476 )

• mice exhibit increased susceptibility to LPS-induced lethality with increased serum levels of IL1b, TNF, IL6, KC, GM-CSF, and IL10 compared with similarly treated wild-type mice

skin inflammation ( J:166476 )

• at 2 weeks of age, most mice exhibit histocytic and/or neutrophilic cellular infiltrates in the skin unlike in wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:166476 )

• mice exhibit increased susceptibility to LPS-induced lethality compared with similarly treated wild-type mice

homeostasis/metabolism

skin edema ( J:166476 )

• at 2 weeks of age

abnormal cytokine level ( J:166476 )

increased circulating interleukin-1 beta level ( J:166476 )

• in LPS-treated mice

increased circulating interleukin-10 level ( J:166476 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:166476 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:166476 )

• in LPS-treated mice

hematopoietic system

increased spleen weight ( J:166476 )

• slight

decreased NK T cell number ( J:166476 )

• mice exhibit reduced CD3+ and CD3+CD8+ T cells compared with wild-type mice

increased NK T cell number ( J:166476 )

• mice exhibit a slight increase in CD3+CD4+ T cells compared with wild-type mice

increased monocyte cell number ( J:166476 )

increased IgA level ( J:166476 )

• 1.5- to 3-fold

integument

skin inflammation ( J:166476 )

• at 2 weeks of age, most mice exhibit histocytic and/or neutrophilic cellular infiltrates in the skin unlike in wild-type mice

sparse hair ( J:166476 )

• at 3 months of age, especially on the ventral surface

disheveled coat ( J:166476 )

• at 3 months of age, especially on the ventral surface

abnormal hair cycle anagen phase ( J:166476 )

• at 3 months of age, more hair follicles are in anagen phase compared to in wild-type mice

• however, no increase in hair follicles in anagen is observed at 2 weeks of age

abnormal skin morphology ( J:166476 )

• at 2 weeks of age, mice exhibit skin necrosis, increased dermal cellularity, hyperkeratosis, skin hyperplasia, inflammatory cell infiltrates, and edema unlike wild-type mice

skin edema ( J:166476 )

• at 2 weeks of age

dermal hyperplasia ( J:166476 )

• at 2 weeks of age

hyperkeratosis ( J:166476 )

• at 2 weeks of age

skin hyperplasia ( J:166476 )

• at 2 weeks of age

growth/size/body

increased spleen weight ( J:166476 )

• slight