Phenotypes Associated with This Genotype

Genotype
MGI:5427085

• Allelic Composition: Polb^tm1.1Jbsw/Polb^tm1.1Jbsw
• Genetic Background: involves: 129/Sv * C57BL/6

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

Polb^tm1.1Jbsw/Polb^tm1.1Jbsw embryos are small

mortality/aging

neonatal lethality, incomplete penetrance ( J:183837 )

• about 60% die within 24h of birth

cellular

abnormal cell cycle ( J:183837 )

• after 5 days in culture 2 fold greater numbers of MEFs accumulate in G2/M compared to wild-type MEFs

increased sensitivity to induced cell death ( J:183837 )

• increased cell death in MEFs following methyl methanesulfonate (MMS) treatment

increased embryonic tissue cell apoptosis ( J:183837 )

• in many organs (heart, lung, stomach, cortex midbrain, kidney, spleen, cerebellum, cortex forebrain, and fetal liver) of embryos

increased kidney apoptosis ( J:183837 )

• in embryos

increased neuron apoptosis ( J:183837 )

• brains show almost a 40-fold increase in apoptosis at E14

increased splenocyte apoptosis ( J:183837 , J:206872 )

• in embryos (J:183837)

• increase in levels of apoptosis in the spleen; TUNEL-positive cells mostly overlap with CD4 T helper cells (J:206872)

increased hepatocyte apoptosis ( J:183837 )

• in fetal livers

decreased cell proliferation ( J:183837 )

• in many organs of embryos

decreased fibroblast proliferation ( J:183837 )

• MEFs double at about half the rate of controls

• growth of MEFs in 5% oxygen yields nearly equivalent proliferation to wild-type MEFs in 20% oxygen

abnormal base-excision repair ( J:183837 )

• deficient in MEFs

• MEFs accumulate BER reaction intermediates

chromosomal instability ( J:183837 )

• significant increase in chromosome fragments, as well as interchromosome and intrachromosome fusions in MEFs

growth/size/body

decreased birth weight ( J:183837 )

• about 33% smaller at birth

decreased body size ( J:183837 )

• survivors remain smaller during the first 3 weeks of life

hematopoietic system

increased splenocyte apoptosis ( J:183837 , J:206872 )

• in embryos (J:183837)

• increase in levels of apoptosis in the spleen; TUNEL-positive cells mostly overlap with CD4 T helper cells (J:206872)

abnormal immunoglobulin heavy chain V(D)J recombination ( J:206872 )

• B cells have shorter CDR3 junctions in the Ig heavy chain compared to wild-type; majority of CDR3 junctions are 31-35 base pairs in length compared to 41-45 base pairs in wild-type mice with many more unidentifiable D regions in the mutant

• the lengths of N/P additions between the rearranged V and D segments are shorter

• however, no differences in length of the Ig light chain junctions or the T receptors and class switch recombination is normal, with no differences in the levels of IgG1, IgG2a, IgG2b or IgG3

abnormal somatic hypermutation frequency ( J:206872 )

• mice show increased frequency of somatic hypermutation; the frequencies of transversions at GC base pairs are most significantly increased, although increases in mutations at A:T base pairs are also increased

• mice exhibit increased levels of mutation in the AID hotspot motifs

increased germinal center B cell number ( J:206872 )

• elevation in numbers of germinal cell B cells and follicular T helper cells in the spleen

increased T-helper 2 cell number ( J:206872 )

• elevation in numbers of follicular T helper cells in the spleen

abnormal spleen germinal center morphology ( J:206872 )

• elevation in numbers of germinal cell B cells and follicular T helper cells in the spleen

increased spleen germinal center number ( J:206872 )

increased IgG level ( J:206872 )

• by 12 months of age, mice show increased levels of IgG localized to the glomeruli

homeostasis/metabolism

abnormal base-excision repair ( J:183837 )

• deficient in MEFs

• MEFs accumulate BER reaction intermediates

immune system

increased splenocyte apoptosis ( J:183837 , J:206872 )

• in embryos (J:183837)

• increase in levels of apoptosis in the spleen; TUNEL-positive cells mostly overlap with CD4 T helper cells (J:206872)

salivary gland inflammation ( J:206872 )

• infiltration of lymphocytes, predominantly T and B cells, in salivary glands of a few mice

abnormal immunoglobulin heavy chain V(D)J recombination ( J:206872 )

• B cells have shorter CDR3 junctions in the Ig heavy chain compared to wild-type; majority of CDR3 junctions are 31-35 base pairs in length compared to 41-45 base pairs in wild-type mice with many more unidentifiable D regions in the mutant

• the lengths of N/P additions between the rearranged V and D segments are shorter

• however, no differences in length of the Ig light chain junctions or the T receptors and class switch recombination is normal, with no differences in the levels of IgG1, IgG2a, IgG2b or IgG3

abnormal somatic hypermutation frequency ( J:206872 )

• mice show increased frequency of somatic hypermutation; the frequencies of transversions at GC base pairs are most significantly increased, although increases in mutations at A:T base pairs are also increased

• mice exhibit increased levels of mutation in the AID hotspot motifs

increased germinal center B cell number ( J:206872 )

• elevation in numbers of germinal cell B cells and follicular T helper cells in the spleen

increased T-helper 2 cell number ( J:206872 )

• elevation in numbers of follicular T helper cells in the spleen

abnormal spleen germinal center morphology ( J:206872 )

• elevation in numbers of germinal cell B cells and follicular T helper cells in the spleen

increased spleen germinal center number ( J:206872 )

increased IgG level ( J:206872 )

• by 12 months of age, mice show increased levels of IgG localized to the glomeruli

enlarged cervical lymph nodes ( J:206872 )

• cervical lymphoadenopathy with significant infiltration of T and B lymphocytes

lymph node inflammation ( J:206872 )

• infiltration of T and B lymphocytes into cervical lymph nodes

increased susceptibility to systemic lupus erythematosus ( J:206872 )

• mice show increased levels of antinuclear antibodies, leading to glomerulonephritis, dermatitis, and cervical lymphadenopathy

increased anti-nuclear antigen antibody level ( J:206872 )

• progressive increase in levels of antinuclear antibodies in blood sera over time

glomerulonephritis ( J:206872 )

dermatitis ( J:206872 )

• increase in prevalence of dermatitis

nervous system

increased neuron apoptosis ( J:183837 )

• brains show almost a 40-fold increase in apoptosis at E14

renal/urinary system

increased kidney apoptosis ( J:183837 )

• in embryos

glomerulonephritis ( J:206872 )

liver/biliary system

increased hepatocyte apoptosis ( J:183837 )

• in fetal livers

digestive/alimentary system

enlarged salivary gland ( J:206872 )

• a few mutants exhibit enlarged salivary glands that have infiltrating lymphocytes, which are predominantly T and B cells

salivary gland inflammation ( J:206872 )

• infiltration of lymphocytes, predominantly T and B cells, in salivary glands of a few mice

endocrine/exocrine glands

enlarged salivary gland ( J:206872 )

• a few mutants exhibit enlarged salivary glands that have infiltrating lymphocytes, which are predominantly T and B cells

salivary gland inflammation ( J:206872 )

• infiltration of lymphocytes, predominantly T and B cells, in salivary glands of a few mice

integument

dermatitis ( J:206872 )

• increase in prevalence of dermatitis

embryo

increased embryonic tissue cell apoptosis ( J:183837 )

• in many organs (heart, lung, stomach, cortex midbrain, kidney, spleen, cerebellum, cortex forebrain, and fetal liver) of embryos

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:206872