Phenotypes associated with this allele

• Allele Symbol: Map3k14^aly
• Allele Name: alymphoplasia
• Allele ID: MGI:1858522
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Map3k14^aly/Map3k14^aly	C57BL/6J-Map3k14^aly	MGI:4361534
hm2	Map3k14^aly/Map3k14^aly	involves: AEJ/GnRk * C57BL/6J	MGI:4361529
hm3	Map3k14^aly/Map3k14^aly	involves: C57BL/6J	MGI:3767418
cx4	Foxn1^nu/Foxn1^nu Map3k14^aly/Map3k14^aly	involves: BALB/cAJcl * C57BL/6J	MGI:4361561
cx5	Map3k14^aly/Map3k14^+ Relb^Tg(H2-K1/GH1)106Bri/Relb^+	involves: C57BL/6 * C57BL/6J	MGI:4361564

Genotype
MGI:4361534

hm1

• Allelic Composition: Map3k14^aly/Map3k14^aly
• Genetic Background: C57BL/6J-Map3k14^aly

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

mortality/aging

premature death ( J:16865 )

immune system

absent lymph nodes ( J:16865 )

increased susceptibility to infection ( J:16865 )

Genotype
MGI:4361529

hm2

• Allelic Composition: Map3k14^aly/Map3k14^aly
• Genetic Background: involves: AEJ/GnRk * C57BL/6J

mortality/aging

mortality/aging ( J:16865 )

N • most mice survive for more than 1 year

immune system

decreased IgA level ( J:16865 , J:54529 )

• undetectable (J:16865)

• mice exhibit undetectable IgA levels unlike in wild-type mice (J:54529)

decreased IgG level ( J:16865 , J:54529 )

• severely (J:16865)

• unchallenged and NP-HGG-challenged mice exhibit reduced IgG levels compared with wild-type mice (J:54529)

decreased IgM level ( J:16865 , J:54529 )

• one third less than in wild-type mice (J:16865)

• mice exhibit reduced IgM levels compared with wild-type mice (J:54529)

abnormal immune system morphology ( J:54529 )

• mice exhibit alymphoplasia

• however, over-expression of the endogenous protein restores lymphocyte development and function

absent thymus corticomedullary boundary ( J:16865 , J:54529 )

• absent (J:16865)

• absent (J:54529)

abnormal lymphocyte morphology ( J:16865 )

• the ratio of B to T cells is reduced compared to in heterozygous mice

abnormal lymphopoiesis ( J:16865 )

• in reconstitution assays, bone marrow has a limited capacity to reconstitute lymphoid tissues compared with wild-type bone marrow

• reconstitution of mice with wild-type bone marrow partially rescues defects in lymphoid tissues

decreased B cell number ( J:54529 )

• in the peritoneal cavity

decreased spleen B cell follicle number ( J:16865 )

• absent

abnormal spleen primary B follicle morphology ( J:54529 )

• absent

absent spleen marginal zone ( J:54529 )

absent follicular dendritic cells ( J:54529 )

absent Peyer's patches ( J:16865 , J:54529 )

absent lymph nodes ( J:16865 , J:54529 )

increased length of allograft survival ( J:16865 )

• mice fail to reject histoincompatible allografts unlike similarly treated wild-type mice

endocrine/exocrine glands

absent thymus corticomedullary boundary ( J:16865 , J:54529 )

• absent (J:16865)

• absent (J:54529)

abnormal mammary gland development ( J:16865 )

♀ • female mice are unable to suckle young

hematopoietic system

absent thymus corticomedullary boundary ( J:16865 , J:54529 )

• absent (J:16865)

• absent (J:54529)

abnormal lymphocyte morphology ( J:16865 )

• the ratio of B to T cells is reduced compared to in heterozygous mice

abnormal lymphopoiesis ( J:16865 )

• in reconstitution assays, bone marrow has a limited capacity to reconstitute lymphoid tissues compared with wild-type bone marrow

• reconstitution of mice with wild-type bone marrow partially rescues defects in lymphoid tissues

decreased B cell number ( J:54529 )

• in the peritoneal cavity

decreased spleen B cell follicle number ( J:16865 )

• absent

abnormal spleen primary B follicle morphology ( J:54529 )

• absent

absent spleen marginal zone ( J:54529 )

decreased IgA level ( J:16865 , J:54529 )

• undetectable (J:16865)

• mice exhibit undetectable IgA levels unlike in wild-type mice (J:54529)

decreased IgG level ( J:16865 , J:54529 )

• severely (J:16865)

• unchallenged and NP-HGG-challenged mice exhibit reduced IgG levels compared with wild-type mice (J:54529)

decreased IgM level ( J:16865 , J:54529 )

• one third less than in wild-type mice (J:16865)

• mice exhibit reduced IgM levels compared with wild-type mice (J:54529)

integument

abnormal mammary gland development ( J:16865 )

♀ • female mice are unable to suckle young

Genotype
MGI:3767418

hm3

• Allelic Composition: Map3k14^aly/Map3k14^aly
• Genetic Background: involves: C57BL/6J

immune system

abnormal immune system morphology ( J:147681 )

abnormal thymus corticomedullary boundary morphology ( J:87993 )

• unclear boundary

abnormal thymus medulla morphology ( J:87993 )

• the thymus medullas is smaller and contains fewer epithelial cells than in heterogyzotes

small thymus ( J:147681 )

thymus cyst ( J:147681 )

• mice exhibit an increase in the number of thymic cysts compared with wild-type mice

• cysts contain some lymphocytes and macrophages and have many projections unlike in wild-type mice

increased eosinophil cell number ( J:135748 )

decreased mast cell number ( J:135748 )

• 2 weeks post-infection with N. brasiliensis, mast cell numbers are decreased compared to in similarly treated wild-type mice

• between 18 and 84 days post-infection with H. polygyrus, mast cell counts in the jejunum are lower than in similarly treated wild-type mice

decreased dendritic cell number ( J:128211 )

• the frequency and number of dendritic cells in the spleen are decreased compared to in wild-type mice

decreased regulatory T cell number ( J:128211 )

• spleens exhibit decreased CD4+ CD25+ regulatory T cells compared with wild-type spleens

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:87993 , J:128211 )

• the spleen and thymus contain reduced percentage an total numbers of CD4+CD25+ regulatory T cells compared to in wild-type mice (J:87993)

• decreased numbers in the spleen (J:128211)

abnormal NK T cell morphology ( J:120659 )

• thymic Valpha14i NKT cells are NK1.1+CD44+ indicating a block late in Valpha14i NKT cell development

decreased NK T cell number ( J:120659 )

• Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice

absent Peyer's patches ( J:120659 )

abnormal immune system physiology ( J:147681 )

decreased IgE level ( J:135748 )

• N. brasiliensis- or H. polygyrus-infected mice fail to exhibit an increase in IgE levels unlike similarly treated wild-type mice

abnormal T cell activation ( J:38580 )

• T cell infiltrates in the salivary gland, lacrimal gland, and kidney exhibit antigen-driven clonal expansion

decreased circulating interferon-gamma level ( J:120659 )

• in alpha-GalCer-treated mice

decreased circulating interleukin-4 level ( J:120659 )

• in alpha-GalCer-treated mice

abnormal dendritic cell physiology ( J:128211 )

• dendritic cells exhibit impaired ability to induce expansion of CD4+ CD25+ regulatory T cells compared with wild-type cells

abnormal dendritic cell antigen presentation ( J:128211 )

• impaired

increased inflammatory response ( J:38580 , J:48224 )

• some mononuclear cells infiltrate focally into the perivascular regions of all organs unlike in wild-type mice (J:38580)

• by 8 to 12 weeks, mice exhibit mild to moderate lymphoid infiltration in every tissue examined with follicle-like lymphoid aggregation in the lungs and less lymphoid aggregation in the gastrointestinal tract unlike in heterozygous mice (J:48224)

lacrimal gland inflammation ( J:38580 )

• mononuclear cells infiltrate around the lacrimal ducts unlike in wild-type mice

pancreas inflammation ( J:48224 )

• after 10 weeks, mice exhibit lymphoid infiltrate around the pancreatic ducts unlike in heterozygous mice

bile duct inflammation ( J:48224 )

• inflammation occurs in intrahepatic, large, and extrahepatic bile ducts

liver inflammation ( J:48224 )

kidney inflammation ( J:38580 )

• mononuclear cells infiltrate around the interstitum in the kidney unlike in wild-type mice

lung inflammation ( J:48224 )

• by 8 to 12 weeks, mice exhibit follicle-like lymphoid aggregation in the lungs unlike in heterozygous mice

increased susceptibility to parasitic infection ( J:135748 )

• 18 days post-infection with Heligmosomoides polygyrus, egg per gram feces (EPG) is increased compared to in similarly treated wild-type mice

• however, EPG at 70 days post-infection with H. polygyrus and N. brasiliensis clearance are normal

• 2 weeks post-infection with Nippostrongylus brasiliensis, mast cell numbers are decreased compared to in similarly treated wild-type mice

• between 18 and 84 days post-infection with H. polygyrus, mast cell counts in the jejunim are lower than in similarly treated wild-type mice

• 18 days after H. polygyrus infection, intestinal goblet cells are decreased compared to in similarly treated wild-type mice

• N. brasiliensis- or H. polygyrus-infected mice fail to exhibit an increase in IgE levels unlike similarly treated wild-type mice

liver/biliary system

bile duct inflammation ( J:48224 )

• inflammation occurs in intrahepatic, large, and extrahepatic bile ducts

liver inflammation ( J:48224 )

abnormal hepatobiliary system morphology ( J:48224 )

• mice exhibit mild to moderate lymphoid infiltration around vessels and the portal areas in the hepatobiliary system unlike in heterozygous mice

• infiltrating lymphoid cells are predominantly CD4+

• 10% to 30% of portal tracts exhibit infiltration of lymphoid cells

abnormal bile duct morphology ( J:48224 )

• bile ducts exhibit pseudopyloric gland metaplasia

• however, no ductopenia nor fibrotic changes are observed

• biliary epithelial cells exhibit a cytoplasmic accumulation of acidophilic substance stained by the anti-cystatin C antibody

bile duct hyperplasia ( J:48224 )

• following inflammation

bile duct proliferation ( J:48224 )

dilated bile duct ( J:48224 )

endocrine/exocrine glands

abnormal salivary gland morphology ( J:38580 , J:48224 )

• mononuclear cells infiltrate around the salivary ducts unlike in wild-type mice (J:38580)

• after 10 weeks, mice exhibit lymphoid infiltrate around the salivary ducts unlike in heterozygous mice (J:48224)

abnormal bile duct morphology ( J:48224 )

• bile ducts exhibit pseudopyloric gland metaplasia

• however, no ductopenia nor fibrotic changes are observed

• biliary epithelial cells exhibit a cytoplasmic accumulation of acidophilic substance stained by the anti-cystatin C antibody

bile duct hyperplasia ( J:48224 )

• following inflammation

bile duct proliferation ( J:48224 )

dilated bile duct ( J:48224 )

abnormal thymus corticomedullary boundary morphology ( J:87993 )

• unclear boundary

abnormal thymus medulla morphology ( J:87993 )

• the thymus medullas is smaller and contains fewer epithelial cells than in heterogyzotes

small thymus ( J:147681 )

thymus cyst ( J:147681 )

• mice exhibit an increase in the number of thymic cysts compared with wild-type mice

• cysts contain some lymphocytes and macrophages and have many projections unlike in wild-type mice

abnormal mammary gland development ( J:117313 )

♀ • mice exhibit an increase in end-bud development compared with heterozygous mice

lacrimal gland inflammation ( J:38580 )

• mononuclear cells infiltrate around the lacrimal ducts unlike in wild-type mice

pancreas inflammation ( J:48224 )

• after 10 weeks, mice exhibit lymphoid infiltrate around the pancreatic ducts unlike in heterozygous mice

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:135748 )

• 18 days after H. polygyrus infection, intestinal goblet cells are decreased compared to in similarly treated wild-type mice

abnormal intestinal epithelium morphology ( J:126867 )

• number of proliferating IECs, and MHC class II expression on IECs are upregulated to a small extent in mutants compared to wild-type controls

abnormal salivary gland morphology ( J:38580 , J:48224 )

• mononuclear cells infiltrate around the salivary ducts unlike in wild-type mice (J:38580)

• after 10 weeks, mice exhibit lymphoid infiltrate around the salivary ducts unlike in heterozygous mice (J:48224)

adipose tissue

abnormal mammary fat pad morphology ( J:117313 )

• mammary gland weight and thickness are decreased compared to in heterozygous mice

• mammary gland fat pad in virgin mice is smaller and thinner than in heterogyzous mice

• during pregnancy, mammary gland fat pad is smaller than in heterozygous mice

decreased mammary fat pad weight ( J:117313 )

renal/urinary system

kidney inflammation ( J:38580 )

• mononuclear cells infiltrate around the interstitum in the kidney unlike in wild-type mice

vision/eye

lacrimal gland inflammation ( J:38580 )

• mononuclear cells infiltrate around the lacrimal ducts unlike in wild-type mice

hematopoietic system

abnormal thymus corticomedullary boundary morphology ( J:87993 )

• unclear boundary

abnormal thymus medulla morphology ( J:87993 )

• the thymus medullas is smaller and contains fewer epithelial cells than in heterogyzotes

small thymus ( J:147681 )

thymus cyst ( J:147681 )

• mice exhibit an increase in the number of thymic cysts compared with wild-type mice

• cysts contain some lymphocytes and macrophages and have many projections unlike in wild-type mice

increased eosinophil cell number ( J:135748 )

decreased mast cell number ( J:135748 )

• 2 weeks post-infection with N. brasiliensis, mast cell numbers are decreased compared to in similarly treated wild-type mice

• between 18 and 84 days post-infection with H. polygyrus, mast cell counts in the jejunum are lower than in similarly treated wild-type mice

decreased dendritic cell number ( J:128211 )

• the frequency and number of dendritic cells in the spleen are decreased compared to in wild-type mice

decreased regulatory T cell number ( J:128211 )

• spleens exhibit decreased CD4+ CD25+ regulatory T cells compared with wild-type spleens

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:87993 , J:128211 )

• the spleen and thymus contain reduced percentage an total numbers of CD4+CD25+ regulatory T cells compared to in wild-type mice (J:87993)

• decreased numbers in the spleen (J:128211)

abnormal NK T cell morphology ( J:120659 )

• thymic Valpha14i NKT cells are NK1.1+CD44+ indicating a block late in Valpha14i NKT cell development

decreased NK T cell number ( J:120659 )

• Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice

decreased IgE level ( J:135748 )

• N. brasiliensis- or H. polygyrus-infected mice fail to exhibit an increase in IgE levels unlike similarly treated wild-type mice

abnormal T cell activation ( J:38580 )

• T cell infiltrates in the salivary gland, lacrimal gland, and kidney exhibit antigen-driven clonal expansion

respiratory system

lung inflammation ( J:48224 )

• by 8 to 12 weeks, mice exhibit follicle-like lymphoid aggregation in the lungs unlike in heterozygous mice

homeostasis/metabolism

decreased circulating interferon-gamma level ( J:120659 )

• in alpha-GalCer-treated mice

decreased circulating interleukin-4 level ( J:120659 )

• in alpha-GalCer-treated mice

integument

abnormal mammary gland development ( J:117313 )

♀ • mice exhibit an increase in end-bud development compared with heterozygous mice

growth/size/body

thymus cyst ( J:147681 )

• mice exhibit an increase in the number of thymic cysts compared with wild-type mice

• cysts contain some lymphocytes and macrophages and have many projections unlike in wild-type mice

cellular

abnormal intestinal goblet cell morphology ( J:135748 )

• 18 days after H. polygyrus infection, intestinal goblet cells are decreased compared to in similarly treated wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary biliary cholangitis		DOID:12236	OMIM:PS109720	J:48224
Sjogren's syndrome		DOID:12894	OMIM:270150	J:38580

Genotype
MGI:4361561

cx4

• Allelic Composition: Foxn1^nu/Foxn1^nu; Map3k14^aly/Map3k14^aly
• Genetic Background: involves: BALB/cAJcl * C57BL/6J

immune system

athymia ( J:96579 )

absent B cells ( J:96579 )

• small intestines lack IgA+ B cells unlike in wild-type mice

decreased T cell number ( J:96579 )

• mature T cells are virtually absent

decreased gamma-delta intraepithelial T cell number ( J:96579 )

• gamma-delta intraepithelial T cell are decreased by a factor of 2 compared to in Foxn1^nu homozygotes

• however, gamma-delta intraepithelial T cells colonize the intestinal epithelia

absent Peyer's patches ( J:96579 )

absent lymph nodes ( J:96579 )

hematopoietic system

athymia ( J:96579 )

absent B cells ( J:96579 )

• small intestines lack IgA+ B cells unlike in wild-type mice

decreased T cell number ( J:96579 )

• mature T cells are virtually absent

decreased gamma-delta intraepithelial T cell number ( J:96579 )

• gamma-delta intraepithelial T cell are decreased by a factor of 2 compared to in Foxn1^nu homozygotes

• however, gamma-delta intraepithelial T cells colonize the intestinal epithelia

endocrine/exocrine glands

athymia ( J:96579 )

Genotype
MGI:4361564

cx5

• Allelic Composition: Map3k14^aly/Map3k14⁺; Relb^{Tg(H2-K1/GH1)106Bri}/Relb⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J

immune system

decreased NK T cell number ( J:120659 )

• Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice and Relb^{Tg(H2-K1/GH1)106Bri} heterozygotes

decreased circulating interferon-gamma level ( J:120659 )

• alpha-GalCer-treated mice exhibit a reduction in IFN-gamma serum levels compared to in single heterozygotes

decreased Peyer's patch number ( J:120659 )

• greater than in Relb^{Tg(H2-K1/GH1)106Bri} heterozygotes

small Peyer's patches ( J:120659 )

• greater than in Relb^{Tg(H2-K1/GH1)106Bri} heterozygotes

homeostasis/metabolism

decreased circulating interferon-gamma level ( J:120659 )

• alpha-GalCer-treated mice exhibit a reduction in IFN-gamma serum levels compared to in single heterozygotes

hematopoietic system

decreased NK T cell number ( J:120659 )

• Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice and Relb^{Tg(H2-K1/GH1)106Bri} heterozygotes