Phenotypes associated with this allele

• Allele Symbol: Rel^tm1Grd
• Allele Name: targeted mutation 1, Steve Gerondakis
• Allele ID: MGI:2179622
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rel^tm1Grd/Rel^tm1Grd	involves: 129S1/Sv	MGI:3799120
hm2	Rel^tm1Grd/Rel^tm1Grd	involves: 129S1/Sv * C57BL/6	MGI:2179631
ht3	Rel^tm1Grd/Rel^+	involves: 129S1/Sv * C57BL/6	MGI:3769513
cx4	Rel^tm1Grd/Rel^tm1Grd Rela^tm1Bal/Rela^tm1Bal	B6.129S-Rel^tm1Grd Rela^tm1Bal	MGI:3799117
cx5	Nfkb1^tm1Bal/Nfkb1^tm1Bal Rel^tm1Grd/Rel^tm1Grd	involves: 129P2/OlaHsd * 129S1/Sv	MGI:3799119
cx6	Rel^tm1Grd/Rel^tm1Grd Rela^tm1Bal/Rela^tm1Bal Tnf^tm1Ljo/Tnf^tm1Ljo	involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJae	MGI:3046865

Genotype
MGI:3799120

hm1

• Allelic Composition: Rel^tm1Grd/Rel^tm1Grd
• Genetic Background: involves: 129S1/Sv

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

immune system

immune system phenotype ( J:113514 )

N • mice exhibit normal dendritic cell development and maturation

Genotype
MGI:2179631

hm2

• Allelic Composition: Rel^tm1Grd/Rel^tm1Grd
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 0.5-2.5% of normal

• B cell colonies are 100-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

• treatment of stimulated B cells with Il2 does not reverse proliferative defect in B cells

decreased T cell proliferation ( J:28435 )

• in response to PMA stimulation, cultured T cells show only ~20% of normal response at 72 hours but in response to ionomycin, response is ~70% of normal

• concanavalin A- or anti-CD3/anti-DC28-stimulated T cells cultured with exogenous Il2 show similar proliferative response to stimulated wild-type cells

abnormal macrophage physiology ( J:37541 )

• resident peritoneal macrophages activated with LPS + interferon gamma show impaired cytotoxic killing ability towards tumor cells in vitro compared to wild-type macrophages

• elicited macrophages from both genotypes show equal cytotoxic abilities

• resident macrophages produce only ~20% of normal nitric oxide levels

abnormal humoral immune response ( J:28435 )

• in response to a T cell-independent antigen (NP-LPS), IgG3 production is marginally reduced at 7 days after immunization, continuing to decrease over the next 14 days

• NP-specific IgG1 production production is 50- to 100-fold lower than in wild-type in response to a T cell-dependent antigen (NP-KHL)

decreased IgG1 level ( J:28435 )

• levels are 100-fold less than in wild-type naive mice

• IgG1 production production is 50- to 100-fold lower than in wild-type in response to a T cell-dependent antigen (NP-KHL)

decreased IgG2a level ( J:28435 )

• levels are almost undetectable in naive mutants

decreased IgG2b level ( J:28435 )

• levels are 6-fold less than in wild-type naive mice

decreased IgG3 level ( J:28435 )

• levels are 4-fold less than in wild-type naive mice

decreased IgM level ( J:28435 )

• levels are 3-fold less than in wild-type naive mice

abnormal cytokine secretion ( J:28435 , J:37541 )

• concanavalin A-stimulated T cells produce Il2 at levels that are 50-fold lower than wild-type; levels are several fold lower than normal in wild-type cultures stimulated with PMA or ionomycin (J:28435)

• with LPS treatment, GM-CSF and G-CSF production by resident macrophages is ~10- and 5-fold greater in wild-type macrophages (J:37541)

• levels of Il6 produced by unstimulated resident and peritoneal macrophages are elevated ~3-fold compared to wild-type; levels of Il6 after LPS stimulation are 3-5-fold higher than stimulated wild-type macrophages (J:37541)

decreased susceptibility to parasitic infection ( J:37541 )

hematopoietic system

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 0.5-2.5% of normal

• B cell colonies are 100-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

• treatment of stimulated B cells with Il2 does not reverse proliferative defect in B cells

decreased T cell proliferation ( J:28435 )

• in response to PMA stimulation, cultured T cells show only ~20% of normal response at 72 hours but in response to ionomycin, response is ~70% of normal

• concanavalin A- or anti-CD3/anti-DC28-stimulated T cells cultured with exogenous Il2 show similar proliferative response to stimulated wild-type cells

decreased IgG1 level ( J:28435 )

• levels are 100-fold less than in wild-type naive mice

• IgG1 production production is 50- to 100-fold lower than in wild-type in response to a T cell-dependent antigen (NP-KHL)

decreased IgG2a level ( J:28435 )

• levels are almost undetectable in naive mutants

decreased IgG2b level ( J:28435 )

• levels are 6-fold less than in wild-type naive mice

decreased IgG3 level ( J:28435 )

• levels are 4-fold less than in wild-type naive mice

decreased IgM level ( J:28435 )

• levels are 3-fold less than in wild-type naive mice

abnormal macrophage physiology ( J:37541 )

• resident peritoneal macrophages activated with LPS + interferon gamma show impaired cytotoxic killing ability towards tumor cells in vitro compared to wild-type macrophages

• elicited macrophages from both genotypes show equal cytotoxic abilities

• resident macrophages produce only ~20% of normal nitric oxide levels

cellular

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 0.5-2.5% of normal

• B cell colonies are 100-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

• treatment of stimulated B cells with Il2 does not reverse proliferative defect in B cells

decreased T cell proliferation ( J:28435 )

• in response to PMA stimulation, cultured T cells show only ~20% of normal response at 72 hours but in response to ionomycin, response is ~70% of normal

• concanavalin A- or anti-CD3/anti-DC28-stimulated T cells cultured with exogenous Il2 show similar proliferative response to stimulated wild-type cells

Genotype
MGI:3769513

ht3

• Allelic Composition: Rel^tm1Grd/Rel⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 14-20% of normal

• B cell colonies are 10-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

abnormal humoral immune response ( J:28435 )

• NP-specific IgG1 production in response to a T cell-dependent antigen (NP-KHL) is intermediate between wild-type and homozygous mice; IgG3 response to NP-LPS is normal

hematopoietic system

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 14-20% of normal

• B cell colonies are 10-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

cellular

decreased B cell proliferation ( J:28435 )

• in culture, splenic B cells respond less efficiently to mitogenic stimulation; proliferative response is 14-20% of normal

• B cell colonies are 10-fold less numerous compared with wild-type cells when splenocytes are seed onto agar cultures containing LPS

Genotype
MGI:3799117

cx4

• Allelic Composition: Rel^tm1Grd/Rel^tm1Grd; Rela^tm1Bal/Rela^tm1Bal
• Genetic Background: B6.129S-Rel^tm1Grd Rela^tm1Bal

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:111325 )

• despite normal appearance up to E12, all mice are dead by E14

hematopoietic system

hematopoietic system phenotype ( J:111325 )

N • despite impaired erythropoeisis, hematopoietic development potential is normal

abnormal monocyte differentiation ( J:111325 )

• increased apoptosis during monocyte differentiation in culture results in a reduced frequency of granulocyte and macrophage colonies compared to cultures from wild-type mice

decreased common myeloid progenitor cell number ( J:111325 )

• 2.5-fold compared to in wild-type mice

abnormal erythropoiesis ( J:111325 )

• mice and irradiated wild-type mice transplanted with mutant mice bone marrow exhibit impaired erythropoiesis

hyperchromasia ( J:111325 )

increased granulocyte number ( J:111325 )

• irradiated mice reconstituted with mutant bone marrow exhibit granulocytosis of fetal liver cells

liver/biliary system

increased hepatocyte apoptosis ( J:111325 )

• most mice exhibit fetal liver cell apoptosis by E13.5

cardiovascular system

internal hemorrhage ( J:111325 )

• most mice exhibit abdominal hemorrhage by E13.5

immune system

abnormal monocyte differentiation ( J:111325 )

• increased apoptosis during monocyte differentiation in culture results in a reduced frequency of granulocyte and macrophage colonies compared to cultures from wild-type mice

increased granulocyte number ( J:111325 )

• irradiated mice reconstituted with mutant bone marrow exhibit granulocytosis of fetal liver cells

cellular

increased hepatocyte apoptosis ( J:111325 )

• most mice exhibit fetal liver cell apoptosis by E13.5

abnormal monocyte differentiation ( J:111325 )

• increased apoptosis during monocyte differentiation in culture results in a reduced frequency of granulocyte and macrophage colonies compared to cultures from wild-type mice

Genotype
MGI:3799119

cx5

• Allelic Composition: Nfkb1^tm1Bal/Nfkb1^tm1Bal; Rel^tm1Grd/Rel^tm1Grd
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

immune system

abnormal immune system physiology ( J:113514 )

• despite normal development of dendritic cells, CD40LG and TNFSF11-induced survival and IL-12 production are abolished

decreased interleukin-12 secretion ( J:113514 )

• cells induced with LPS produce less IL-12 than similarly treated wild-type cells

Genotype
MGI:3046865

cx6

• Allelic Composition: Rel^tm1Grd/Rel^tm1Grd; Rela^tm1Bal/Rela^tm1Bal; Tnf^tm1Ljo/Tnf^tm1Ljo
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJae

mortality/aging

neonatal lethality, complete penetrance ( J:91366 )

• triple homozygous pups die within 12 hours of birth

cellular

abnormal cell cycle ( J:91366 )

• transit-amplifying epidermal cells display a delay in G₁/S phase progression

decreased cell proliferation ( J:91366 )

• transit-amplifying epidermal cells display reduced proliferation

embryo

decreased embryo size ( J:91366 )

• triple homozygous embryos are about 30% smaller compared to littermate controls

growth/size/body

decreased embryo size ( J:91366 )

• triple homozygous embryos are about 30% smaller compared to littermate controls

integument

abnormal hair follicle placode formation ( J:91366 )

• about a 24 hour delay in hair placode formation is seen compared to control littermates

underdeveloped hair follicles ( J:91366 )

• at E18 the hair follicles that are present are only rudimentary buds lacking hair shafts

decreased hair follicle number ( J:91366 )

• at E18, 70% fewer hair follicles are present compared to control littermates

abnormal epidermal layer morphology ( J:91366 )

abnormal epidermis stratum basale morphology ( J:91366 )

• the cells in the basal cell layer are organized differently and the basal cell profile area is reduced by about 33%

abnormal keratinocyte morphology ( J:91366 )

• the number of differentiating keratinocytes is reduced

thin epidermis ( J:91366 )

• the epidermis is significantly thinner