Phenotypes associated with this allele

• Allele Symbol: Mbd2^tm1Bh
• Allele Name: targeted mutation 1, Brian Hendrich
• Allele ID: MGI:2388002
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mbd2^tm1Bh/Mbd2^tm1Bh	involves: 129P2/OlaHsd * C57BL/6	MGI:3579837
hm2	Mbd2^tm1Bh/Mbd2^tm1Bh	NOD.129P2(B6)-Mbd2^tm1Bh	MGI:7276257
cx3	Mbd2^tm1Bh/Mbd2^tm1Bh Mbd3^tm1Bh/Mbd3^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3579841
cx4	Mbd2^tm1Bh/Mbd2^tm1Bh Mecp2^tm1.1Bird/Y	involves: 129P2/OlaHsd * C57BL/6	MGI:3624722
cx5	Apc^Min/Apc^+ Mbd2^tm1Bh/Mbd2^tm1Bh	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:3579838
cx6	Apc^Min/Apc^+ Mbd2^tm1Bh/Mbd2^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:3579839

Genotype
MGI:3579837

hm1

• Allelic Composition: Mbd2^tm1Bh/Mbd2^tm1Bh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

reproductive system

decreased litter size ( J:68356 )

• average litter size half that of controls

behavior/neurological

abnormal maternal nurturing ( J:68356 )

♀ • small size of progeny independent of genotype of pups

♀ • size difference most pronounced 13-19 days after birth

♀ • pups make up the size discrepancy after weaning

abnormal pup retrieval ( J:68356 )

♀ • pup retrieval for the first pup retrieved is marginally slower than normal

♀ • subsequent pup retrievals are significantly slower than normal

Genotype
MGI:7276257

hm2

• Allelic Composition: Mbd2^tm1Bh/Mbd2^tm1Bh
• Genetic Background: NOD.129P2(B6)-Mbd2^tm1Bh

homeostasis/metabolism

abnormal homeostasis ( J:323838 )

• mice show a decrease of plasma c-peptide levels compared to NOD/ShiLtJ controls

hyperglycemia ( J:323838 )

• mice show an increase in incidence of spontaneous diabetes, with increased levels of blood glucose and an earlier onset of type I diabetes, compared to NOD/ShiLtJ controls

immune system

increased T cell proliferation ( J:323838 )

• isolated CD4 T cells costimulated with anti-CD3/CD28 show increased CD4 T cell proliferation without an impact on T cell apoptosis

salivary gland inflammation ( J:323838 )

• mice exhibit increased infiltration of lymphocytes in the salivary gland

• however, no evidence of inflammatory infiltration is seen in the colon, lung, kidney, liver or heart

insulitis ( J:323838 )

• mice exhibit more islets with invasive insulitis at both early prediabetic stage (5-6 weeks) and advanced diabetic stage 12 (12-15 weeks) compared to control NOD/ShiLtJ mice

enlarged spleen ( J:323838 )

• mice exhibit splenomegaly, suggesting a more severe autoimmune response than in NOD/ShiLtJ controls

abnormal effector T cell morphology ( J:323838 )

• although the proportions of CD4 T cells and CD8 T cells in the pancreatic lymph nodes are comparable to controls, mice exhibit a higher proportion of CD44^hi CD62L^lo effector and lower proportion of CD44^lo CD62L^hi nave T cells in total CD4 T cells

increased T-helper 1 cell number ( J:323838 )

• the frequency of CD4+/IFN-gamma+ (Th1) cells is much higher than in controls

increased T-helper 2 cell number ( J:323838 )

• mice show a modest increase of CD4+/IL-4+ (Th2) cells, but without a perceptible change in CD4+/IL-17A+ (Th17) and CD4+/Foxp3+ (Treg) subsets compared to controls

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:323838 )

• frequency of IFN-gamma+ cytotoxic CD8 T cells is higher than in controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:323838 )

• isolated CD4 T cells costimulated with anti-CD3/CD28 show increased CD4 T cell proliferation without an impact on T cell apoptosis, and higher amounts of type I cytokine expression, including IFN-gamma, GM-CSF, and TNF-alpha

• isolated CD4 T cells produce higher IFN-gamma levels under non-polarized conditions

enlarged lymph nodes ( J:323838 )

• mice exhibit pancreatic lymphadenopathy, suggesting a more severe autoimmune response than in NOD/ShiLtJ controls

digestive/alimentary system

salivary gland inflammation ( J:323838 )

• mice exhibit increased infiltration of lymphocytes in the salivary gland

• however, no evidence of inflammatory infiltration is seen in the colon, lung, kidney, liver or heart

endocrine/exocrine glands

salivary gland inflammation ( J:323838 )

• mice exhibit increased infiltration of lymphocytes in the salivary gland

• however, no evidence of inflammatory infiltration is seen in the colon, lung, kidney, liver or heart

abnormal pancreatic islet morphology ( J:323838 )

• mice show numerous shrunk islets with a reduction of insulin-positive cells compared to controls which show more structured islets and insulin-secreting beta cells

insulitis ( J:323838 )

• mice exhibit more islets with invasive insulitis at both early prediabetic stage (5-6 weeks) and advanced diabetic stage 12 (12-15 weeks) compared to control NOD/ShiLtJ mice

growth/size/body

enlarged spleen ( J:323838 )

• mice exhibit splenomegaly, suggesting a more severe autoimmune response than in NOD/ShiLtJ controls

hematopoietic system

increased T cell proliferation ( J:323838 )

• isolated CD4 T cells costimulated with anti-CD3/CD28 show increased CD4 T cell proliferation without an impact on T cell apoptosis

enlarged spleen ( J:323838 )

• mice exhibit splenomegaly, suggesting a more severe autoimmune response than in NOD/ShiLtJ controls

abnormal effector T cell morphology ( J:323838 )

• although the proportions of CD4 T cells and CD8 T cells in the pancreatic lymph nodes are comparable to controls, mice exhibit a higher proportion of CD44^hi CD62L^lo effector and lower proportion of CD44^lo CD62L^hi nave T cells in total CD4 T cells

increased T-helper 1 cell number ( J:323838 )

• the frequency of CD4+/IFN-gamma+ (Th1) cells is much higher than in controls

increased T-helper 2 cell number ( J:323838 )

• mice show a modest increase of CD4+/IL-4+ (Th2) cells, but without a perceptible change in CD4+/IL-17A+ (Th17) and CD4+/Foxp3+ (Treg) subsets compared to controls

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:323838 )

• frequency of IFN-gamma+ cytotoxic CD8 T cells is higher than in controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:323838 )

• isolated CD4 T cells costimulated with anti-CD3/CD28 show increased CD4 T cell proliferation without an impact on T cell apoptosis, and higher amounts of type I cytokine expression, including IFN-gamma, GM-CSF, and TNF-alpha

• isolated CD4 T cells produce higher IFN-gamma levels under non-polarized conditions

cellular

increased T cell proliferation ( J:323838 )

• isolated CD4 T cells costimulated with anti-CD3/CD28 show increased CD4 T cell proliferation without an impact on T cell apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:323838

Genotype
MGI:3579841

cx3

• Allelic Composition: Mbd2^tm1Bh/Mbd2^tm1Bh; Mbd3^tm1Bh/Mbd3⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:68356 )

• surviving heterozygotes reduced by 30% from expected

Genotype
MGI:3624722

cx4

• Allelic Composition: Mbd2^tm1Bh/Mbd2^tm1Bh; Mecp2^tm1.1Bird/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:67910 )

♂ • exhibit the same mortality as single homozygous Mecp2 null mice

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:67910 )

♂ • exhibit the same onset of Rett-like syndrome symptoms and mortality as single homozygous Mecp2 null mice

Genotype
MGI:3579838

cx5

• Allelic Composition: Apc^Min/Apc⁺; Mbd2^tm1Bh/Mbd2^tm1Bh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

mortality/aging

mortality/aging ( J:83087 )

N • homozygotes survive significantly longer than mice only heterozygous for Apc^Min

neoplasm

decreased tumor growth/size ( J:83087 )

• tumors present are smaller in size

decreased tumor incidence ( J:83087 )

• at death, mice have a 10 fold reduction in adenomas

• adenomas that are present are restricted to Brunners gland and the distal 2 cm of the large intestine

Genotype
MGI:3579839

cx6

• Allelic Composition: Apc^Min/Apc⁺; Mbd2^tm1Bh/Mbd2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:83087 )

• although survival is reduced, they live longer than mice only heterozygous for Apc^Min

neoplasm

decreased tumor incidence ( J:83087 )

• tumor repression specific to the small intestine