Phenotypes associated with this allele

• Allele Symbol: Bhlhe40^tm1Tan
• Allele Name: targeted mutation 1, Reshma Taneja
• Allele ID: MGI:2180488
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bhlhe40^tm1Tan/Bhlhe40^tm1Tan	B6.129-Bhlhe40^tm1Tan	MGI:3805471
hm2	Bhlhe40^tm1Tan/Bhlhe40^tm1Tan	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:2657276
cx3	Bhlhe40^tm1Tan/Bhlhe40^tm1Tan Bhlhe41^tm1Mjro/Bhlhe41^tm1Mjro	B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro	MGI:3805470
cx4	Bhlhe40^tm1Tan/Bhlhe40^tm1Tan Bhlhe41^tm1Mjro/Bhlhe41^+	B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro	MGI:3805472
cx5	Bhlhe40^tm1Tan/Bhlhe40^+ Bhlhe41^tm1Mjro/Bhlhe41^tm1Mjro	B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro	MGI:3805473

Genotype
MGI:3805471

hm1

• Allelic Composition: Bhlhe40^tm1Tan/Bhlhe40^tm1Tan
• Genetic Background: B6.129-Bhlhe40^tm1Tan

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

behavior/neurological

delayed circadian behavior phase ( J:138240 )

• when mice are subjected to light pulses following constant darkness, the transition phase is prolonged compared to in wild-type mice

• following an 8 hours light dark cycle delay (experimental jet lag), mice exhibit a delayed behavioral re-entrainment compared to wild-type mice

• however, the photic phase response curve and rhythmicity of wheel running during light dark and dark dark phases is normal

Genotype
MGI:2657276

hm2

• Allelic Composition: Bhlhe40^tm1Tan/Bhlhe40^tm1Tan
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

immune system

thymus hyperplasia ( J:72651 )

• in aging mice

spleen hyperplasia ( J:72651 )

• in aging mice

increased spleen germinal center number ( J:72651 )

increased spleen white pulp amount ( J:72651 )

abnormal immune system cell morphology ( J:72651 )

• spontaneous activation of B and T cells

abnormal CD4-positive T cell differentiation ( J:72651 )

• naive CD4+ T cells cultured under both TH1 and TH2 polarizing conditions produce less IFN-gamma and IL-4, indicating a defective differentiation into effector cells

increased double-negative T cell number ( J:72651 )

• 18-fold increase in double-negative thymocyte population at 6-8 months of age

decreased double-positive T cell number ( J:72651 )

• 95% decrease in double-positive thymocytes at 6-8 months of age

increased CD4-positive, alpha-beta T cell number ( J:72651 )

• 2- to 4-fold increase in mature CD4+ single-positive cells

increased CD8-positive, alpha-beta T cell number ( J:72651 )

• 2- to 4-fold increase in mature CD8+ single-positive cells

abnormal lymph node germinal center morphology ( J:72651 )

• aging mice exhibit increased germinal centers in lymph nodes

lymph node hyperplasia ( J:72651 )

• aging mutants show lymph node hyperplasia

abnormal immune system physiology ( J:72651 )

• hyporesponsive immune system

increased IgE level ( J:72651 )

• elevation of IgE in lymphoid tissue

increased IgG1 level ( J:72651 )

• elevation of IgG1 in lymphoid tissue

abnormal CD4-positive, alpha-beta T cell physiology ( J:72651 )

• effector CD4+ T cells from 8-10 week old mutants exhibit greater resistance to antigen induced cell death (AICD)

• restimulation of activated CD4+ T cells in the presence of activated B cells results in an increase in B cell survival, suggesting that CD4+ T cells cannot eliminate activated B cells efficiently

abnormal T cell activation ( J:72651 )

• draining lymph node cells from KLH immunized mutants proliferate at a lower rate than wild-type cells and show a reduction in IL-2 and TH1-type cytokine production

decreased T cell proliferation ( J:72651 )

• CD4+ T cells proiferate less efficiently than wild-type cells upon stimulation with a low dose of anti-CD3 and anti-CD28 antibodies

decreased interleukin-2 secretion ( J:72651 )

• activated CD4+ T cells show a 70% reduction in IL-2 production

abnormal susceptibility to autoimmune disorder ( J:72651 )

• mutants develop a chronic systemic lupus-like autoimmune disease with age

increased anti-nuclear antigen antibody level ( J:72651 )

• circulating autoreactive nuclear antibodies are present in aging mutants

hematopoietic system

thymus hyperplasia ( J:72651 )

• in aging mice

spleen hyperplasia ( J:72651 )

• in aging mice

abnormal CD4-positive T cell differentiation ( J:72651 )

• naive CD4+ T cells cultured under both TH1 and TH2 polarizing conditions produce less IFN-gamma and IL-4, indicating a defective differentiation into effector cells

increased double-negative T cell number ( J:72651 )

• 18-fold increase in double-negative thymocyte population at 6-8 months of age

decreased double-positive T cell number ( J:72651 )

• 95% decrease in double-positive thymocytes at 6-8 months of age

increased CD4-positive, alpha-beta T cell number ( J:72651 )

• 2- to 4-fold increase in mature CD4+ single-positive cells

increased CD8-positive, alpha-beta T cell number ( J:72651 )

• 2- to 4-fold increase in mature CD8+ single-positive cells

increased spleen germinal center number ( J:72651 )

increased spleen white pulp amount ( J:72651 )

increased IgE level ( J:72651 )

• elevation of IgE in lymphoid tissue

increased IgG1 level ( J:72651 )

• elevation of IgG1 in lymphoid tissue

abnormal CD4-positive, alpha-beta T cell physiology ( J:72651 )

• effector CD4+ T cells from 8-10 week old mutants exhibit greater resistance to antigen induced cell death (AICD)

• restimulation of activated CD4+ T cells in the presence of activated B cells results in an increase in B cell survival, suggesting that CD4+ T cells cannot eliminate activated B cells efficiently

abnormal T cell activation ( J:72651 )

• draining lymph node cells from KLH immunized mutants proliferate at a lower rate than wild-type cells and show a reduction in IL-2 and TH1-type cytokine production

decreased T cell proliferation ( J:72651 )

• CD4+ T cells proiferate less efficiently than wild-type cells upon stimulation with a low dose of anti-CD3 and anti-CD28 antibodies

renal/urinary system

abnormal renal glomerulus morphology ( J:72651 )

• aging mice exhibit hypercellularity and proteinaceous deposits in glomeruli

endocrine/exocrine glands

thymus hyperplasia ( J:72651 )

• in aging mice

growth/size/body

spleen hyperplasia ( J:72651 )

• in aging mice

cellular

decreased T cell proliferation ( J:72651 )

• CD4+ T cells proiferate less efficiently than wild-type cells upon stimulation with a low dose of anti-CD3 and anti-CD28 antibodies

Genotype
MGI:3805470

cx3

• Allelic Composition: Bhlhe40^tm1Tan/Bhlhe40^tm1Tan; Bhlhe41^tm1Mjro/Bhlhe41^tm1Mjro
• Genetic Background: B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro

behavior/neurological

abnormal circadian behavior ( J:138240 )

• free-running period length in constant darkness following light dark entrainment is lengthened compared to in wild-type mice

• however, rhythmicity of wheel running during light dark and dark dark phases is normal

delayed circadian behavior phase ( J:138240 )

• phase shift responses are lengthened

• however, the photic phase response curve is normal

• following an 8 hours light dark cycle delay (experimental jet lag), mice exhibit significant delayed behavioral re-entrainment compared to wild-type mice

Genotype
MGI:3805472

cx4

• Allelic Composition: Bhlhe40^tm1Tan/Bhlhe40^tm1Tan; Bhlhe41^tm1Mjro/Bhlhe41⁺
• Genetic Background: B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro

behavior/neurological

abnormal circadian behavior ( J:138240 )

• free-running period length in constant darkness following light dark entrainment is lengthened compared to in wild-type mice

• however, rhythmicity of wheel running during light dark and dark dark phases is normal

delayed circadian behavior phase ( J:138240 )

• following an 8 hours light dark cycle delay (experimental jet lag), mice exhibit significant delayed behavioral re-entrainment compared to wild-type mice that is not greater than in Bhlhb2^tm1Tan homozygotes

Genotype
MGI:3805473

cx5

• Allelic Composition: Bhlhe40^tm1Tan/Bhlhe40⁺; Bhlhe41^tm1Mjro/Bhlhe41^tm1Mjro
• Genetic Background: B6.129-Bhlhe40^tm1Tan Bhlhe41^tm1Mjro

behavior/neurological

abnormal circadian behavior ( J:138240 )

• free-running period length in constant darkness following light dark entrainment is lengthened compared to in wild-type mice

• however, rhythmicity of wheel running during light dark and dark dark phases is normal

delayed circadian behavior phase ( J:138240 )

• following an 8 hours light dark cycle delay (experimental jet lag), mice exhibit significant delayed behavioral re-entrainment compared to wild-type mice that is not greater than in Bhlhb2^tm1Tan homozygotes