Phenotypes associated with this allele

• Allele Symbol: Paxx^em1Spj
• Allele Name: endonuclease-mediated mutation 1, Stephen P Jackson
• Allele ID: MGI:5822837
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Paxx^em1Spj/Paxx^em1Spj	C57BL/6NTac-Paxx^em1Spj	MGI:5829786
cx2	Paxx^em1Spj/Paxx^em1Spj Lig4^tm1Fwa/Lig4^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:5829792
cx3	Paxx^em1Spj/Paxx^em1Spj Nhej1^tm1Fwa/Nhej1^tm1Fwa	involves: 129S6/SvEvTac * C57BL/6NTac	MGI:5827971
cx4	Atm^tm1Awb/Atm^tm1Awb Paxx^em1Spj/Paxx^em1Spj	involves: A/J * C57BL/6NTac	MGI:5829795
cx5	Paxx^em1Spj/Paxx^em1Spj Xrcc5^tm1Nus/Xrcc5^tm1Nus	involves: C57BL/6 * C57BL/6NTac	MGI:5829790

Genotype
MGI:5829786

hm1

• Allelic Composition: Paxx^em1Spj/Paxx^em1Spj
• Genetic Background: C57BL/6NTac-Paxx^em1Spj

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

mortality/aging

increased mortality induced by gamma-irradiation ( J:236776 )

• following exposure to 5 Gy of whole-body gamma radiation, mice (>12 weeks of age) show significantly increased lethality relative to wild-type controls, although this is not as dramatic as that observed in Atm^tm1Awb homozygotes

immune system

immune system phenotype ( J:236776 )

N • mice show no overt immunodeficiency and mount a normal humoral response upon immunization with purified fragment C of tetanus toxin relative to wild-type controls

N • no defects in class switch recombination are observed

increased mature B cell number ( J:236776 )

• mice exhibit a small increase in the number and percentage of mature B cells in the bone marrow

decreased B cell number ( J:236776 )

• significant reduction of B cell number in spleen

decreased transitional stage B cell number ( J:236776 )

• mild reduction of transitional B cell number in spleen

decreased follicular B cell number ( J:236776 )

• significant reduction of follicular B cell number in spleen

decreased T cell number ( J:236776 )

• significant reduction of T cell number in spleen

• however, T cell development in the thymus is normal

decreased CD4-positive, alpha-beta T cell number ( J:236776 )

• significant reduction of CD4+ T cell number in spleen

decreased CD8-positive, alpha-beta T cell number ( J:236776 )

• mild reduction of CD8+ T cell number in spleen

decreased splenocyte number ( J:236776 )

• mice show a significant reduction of total cell numbers in the spleen, but not in the thymus or bone marrow, relative to wild-type controls

• splenic cell reduction is mainly due to decreased B cell and T cell populations

• however, splenic marginal zone B cell numbers and NK cell numbers are normal

hematopoietic system

increased mature B cell number ( J:236776 )

• mice exhibit a small increase in the number and percentage of mature B cells in the bone marrow

decreased B cell number ( J:236776 )

• significant reduction of B cell number in spleen

decreased transitional stage B cell number ( J:236776 )

• mild reduction of transitional B cell number in spleen

decreased follicular B cell number ( J:236776 )

• significant reduction of follicular B cell number in spleen

decreased T cell number ( J:236776 )

• significant reduction of T cell number in spleen

• however, T cell development in the thymus is normal

decreased CD4-positive, alpha-beta T cell number ( J:236776 )

• significant reduction of CD4+ T cell number in spleen

decreased CD8-positive, alpha-beta T cell number ( J:236776 )

• mild reduction of CD8+ T cell number in spleen

decreased splenocyte number ( J:236776 )

• mice show a significant reduction of total cell numbers in the spleen, but not in the thymus or bone marrow, relative to wild-type controls

• splenic cell reduction is mainly due to decreased B cell and T cell populations

• however, splenic marginal zone B cell numbers and NK cell numbers are normal

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:236776 )

• following exposure to 5 Gy of whole-body gamma radiation, mice (>12 weeks of age) show significantly increased lethality relative to wild-type controls, although this is not as dramatic as that observed in Atm^tm1Awb homozygotes

cellular

cellular phenotype ( J:236776 )

N • mice show no increased genomic instability, as determined by micronucleus formation

neoplasm

neoplasm ( J:236776 )

N • mice show no increased tumor predisposition up to 400 days of age

Genotype
MGI:5829792

cx2

• Allelic Composition: Paxx^em1Spj/Paxx^em1Spj; Lig4^tm1Fwa/Lig4^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

mortality/aging

prenatal lethality, complete penetrance ( J:236776 )

• no mice are born, similar to single Lig4^tm1Fwa homozygotes

Genotype
MGI:5827971

cx3

• Allelic Composition: Paxx^em1Spj/Paxx^em1Spj; Nhej1^tm1Fwa/Nhej1^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NTac

Small body size, absence of thymus, and small spleen in Paxx^em1Spj/Paxx^em1Spj Nhej1^tm1Fwa/Nhej1^tm1Fwa mice

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:236776 )

• although double homozygotes are present at normal Mendelian frequencies at E14.5, a significant number of them are dead by E18.5

postnatal lethality, incomplete penetrance ( J:236776 )

• double homozygotes are severely underrepresented at 2 weeks of age, with only one mouse identified out of 25 expected

growth/size/body

decreased embryo size ( J:236776 )

• >50% of double mutant embryos are smaller than controls by E10.5

• however, somite numbers are normal at E10.5

decreased birth body size ( J:236776 )

• single born double mutant mouse is smaller than normal at birth

decreased body size ( J:236776 )

• single born double mutant mouse is smaller at 5 days of age and fails to thrive by 10 days of age

decreased body weight ( J:236776 )

• body weight of single born double mutant mouse is significantly reduced at 10 days of age

decreased fetal size ( J:236776 )

• double mutant fetuses are smaller than controls at E14.5

decreased fetal weight ( J:236776 )

• by E18.5, only a few double mutant fetuses are viable but show reduced body weight

immune system

athymia ( J:236776 )

• upon necropsy, single born double mutant mouse exhibited no thymus

abnormal thymus involution ( J:236776 )

• few double mutants surviving to E18.5 exhibit drastic involution of the thymus, unlike single Nhej1^tm1Fwa homozygotes

absent lymphocyte ( J:236776 )

• no lymphocytes are recovered upon red blood cell lysis

small spleen ( J:236776 )

• upon necropsy, single born double mutant mouse exhibited a microspleen

• few double mutants surviving to E18.5 exhibit much smaller spleens than controls

decreased spleen weight ( J:236776 )

• spleen weight of single born double mutant mouse is significantly reduced relative to body weight at 10 days of age

decreased splenocyte number ( J:236776 )

• single born double mutant mouse shows a significant decrease in splenic cell counts relative to body weight at 10 days of age

hematopoietic system

athymia ( J:236776 )

• upon necropsy, single born double mutant mouse exhibited no thymus

abnormal thymus involution ( J:236776 )

• few double mutants surviving to E18.5 exhibit drastic involution of the thymus, unlike single Nhej1^tm1Fwa homozygotes

absent lymphocyte ( J:236776 )

• no lymphocytes are recovered upon red blood cell lysis

small spleen ( J:236776 )

• upon necropsy, single born double mutant mouse exhibited a microspleen

• few double mutants surviving to E18.5 exhibit much smaller spleens than controls

decreased spleen weight ( J:236776 )

• spleen weight of single born double mutant mouse is significantly reduced relative to body weight at 10 days of age

decreased splenocyte number ( J:236776 )

• single born double mutant mouse shows a significant decrease in splenic cell counts relative to body weight at 10 days of age

cellular

increased neural tube apoptosis ( J:236776 )

• at E10.5 and E14.5, double mutants exhibit increased neural tube apoptosis, as shown by accumulation of cleaved caspase 3, especially in the cortical plate region of the cerebral cortex

• however, no increased apoptosis is observed in the skin, liver, heart or lung

chromosomal instability ( J:236776 )

• at E10.5 and E14.5, double mutants exhibit a significant increase in gammaH2AX-positive cells in the CNS (neural tube) relative to controls, indicating increased genomic instability

• mild genomic instability is also noted in the heart and skin

nervous system

increased neural tube apoptosis ( J:236776 )

• at E10.5 and E14.5, double mutants exhibit increased neural tube apoptosis, as shown by accumulation of cleaved caspase 3, especially in the cortical plate region of the cerebral cortex

• however, no increased apoptosis is observed in the skin, liver, heart or lung

embryo

decreased embryo size ( J:236776 )

• >50% of double mutant embryos are smaller than controls by E10.5

• however, somite numbers are normal at E10.5

endocrine/exocrine glands

athymia ( J:236776 )

• upon necropsy, single born double mutant mouse exhibited no thymus

abnormal thymus involution ( J:236776 )

• few double mutants surviving to E18.5 exhibit drastic involution of the thymus, unlike single Nhej1^tm1Fwa homozygotes

Genotype
MGI:5829795

cx4

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Paxx^em1Spj/Paxx^em1Spj
• Genetic Background: involves: A/J * C57BL/6NTac

mortality/aging

mortality/aging ( J:236776 )

N • double homozygotes are born at the expected Mendelian frequencies and closely resemble single Atm^tm1Awb homozygotes

immune system

abnormal class switch recombination ( J:236776 )

• splenic B cells show no further defect in class switch recombination relative to that in single Atm^tm1Awb homozygotes

decreased B cell number ( J:236776 )

• mice show a similar reduction of B cell number in spleen relative to single Atm^tm1Awb homozygotes

decreased T cell number ( J:236776 )

• mice show a similar reduction of T cell number in spleen relative to single Atm^tm1Awb homozygotes

decreased splenocyte number ( J:236776 )

• at 6-8 weeks of age, mice show a similar reduction of total cell numbers in spleen relative to single Atm^tm1Awb homozygotes

hematopoietic system

abnormal class switch recombination ( J:236776 )

• splenic B cells show no further defect in class switch recombination relative to that in single Atm^tm1Awb homozygotes

decreased B cell number ( J:236776 )

• mice show a similar reduction of B cell number in spleen relative to single Atm^tm1Awb homozygotes

decreased T cell number ( J:236776 )

• mice show a similar reduction of T cell number in spleen relative to single Atm^tm1Awb homozygotes

decreased splenocyte number ( J:236776 )

• at 6-8 weeks of age, mice show a similar reduction of total cell numbers in spleen relative to single Atm^tm1Awb homozygotes

Genotype
MGI:5829790

cx5

• Allelic Composition: Paxx^em1Spj/Paxx^em1Spj; Xrcc5^tm1Nus/Xrcc5^tm1Nus
• Genetic Background: involves: C57BL/6 * C57BL/6NTac

mortality/aging

postnatal lethality, incomplete penetrance ( J:236776 )

• at 2 weeks of age, double homozygotes are significantly underrepresented relative to wild-type controls, but are found at ratios similar to those of single Xrcc5^tm1Nus homozygotes

• no overt phenotypes are observed relative to single Xrcc5^tm1Nus homozygotes