Phenotypes Associated with This Genotype

Genotype
MGI:3656003

cx7

• Allelic Composition: Lig4^tm1Fwa/Lig4^tm1Fwa; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

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

mortality/aging

premature death ( J:63078 )

• mice appear normal until 6 weeks of age, when survival drops precipitously

prenatal lethality, incomplete penetrance ( J:63078 )

• embryonic lethality is dramatically abrogated in double mutants (34/369 double null offspring) compared to nearly total lethality with Lig4-deficiency alone (8/369 observed)

• numbers of double heterozygotes observed are similar to expected numbers

growth/size/body

decreased body weight ( J:63078 )

• postnatally, mice are smaller (only 50% of control littermate weight) than wild-type or doubly-heterozygous littermates

cellular

increased cellular sensitivity to ionizing radiation ( J:63078 )

• cells are markedly sensitive to radiation

decreased neuron apoptosis ( J:63078 )

• low levels of pyknotic nuclei are observed between E12.5 and E14.5, indicating significant rescue of neuronal apoptosis which is seen in Lig4-deficient embryos

increased fibroblast proliferation ( J:63078 )

• cultured MEFs show significantly high rates of doubling compared to Lig4-deficient mice and are close to wild-type levels

immune system

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice

increased B cell number ( J:63078 )

• moderately increased B220+ CD43+ cell numbers are seen in bone marrow compared to Lig4-null, Trp53-heterozygous mice

hematopoietic system

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice

increased B cell number ( J:63078 )

• moderately increased B220+ CD43+ cell numbers are seen in bone marrow compared to Lig4-null, Trp53-heterozygous mice

nervous system

decreased neuron apoptosis ( J:63078 )

• low levels of pyknotic nuclei are observed between E12.5 and E14.5, indicating significant rescue of neuronal apoptosis which is seen in Lig4-deficient embryos

neoplasm

increased lymphoma incidence ( J:63078 )

• almost all (15/16) mice develop aggressive widely disseminated lymphoma which infiltrates the spleen, bone marrow, lymph nodes and thymus

endocrine/exocrine glands

decreased thymocyte number ( J:63078 )

• little rescue of thymocyte number is observed compared to Lig4-deficient mice