Phenotypes associated with this allele

• Allele Symbol: Atm^tm1Awb
• Allele Name: targeted mutation 1, Anthony Wynshaw Boris
• Allele ID: MGI:1857132
• Summary: 23 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atm^tm1Awb/Atm^tm1Awb	129S6/SvEvTac-Atm^tm1Awb	MGI:5565477
hm2	Atm^tm1Awb/Atm^tm1Awb	129S6/SvEvTac-Atm^tm1Awb/J	MGI:6110013
hm3	Atm^tm1Awb/Atm^tm1Awb	A.129S6-Atm^tm1Awb	MGI:5565476
hm4	Atm^tm1Awb/Atm^tm1Awb	A.129S6-Atm^tm1Awb/J	MGI:5829788
hm5	Atm^tm1Awb/Atm^tm1Awb	B6.129S6-Atm^tm1Awb	MGI:5565475
hm6	Atm^tm1Awb/Atm^tm1Awb	CByJ.129S6-Atm^tm1Awb	MGI:5565474
hm7	Atm^tm1Awb/Atm^tm1Awb	either: 129S6/SvEvTac-Atm^tm1Awb or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2175703
hm8	Atm^tm1Awb/Atm^tm1Awb	either: (129S6/SvEvTac-Atm^tm1Awb x A.129S6-Atm^tm1Awb)F1 or (A.129S6-Atm^tm1Awb x 129S6/SvEvTac-Atm^tm1Awb)F1	MGI:5565479
hm9	Atm^tm1Awb/Atm^tm1Awb	either: (129S6/SvEvTac-Atm^tm1Awb x B6.129S6-Atm^tm1Awb)F1 or (B6.129S6-Atm^tm1Awb x 129S6/SvEvTac-Atm^tm1Awb)F1	MGI:5565478
hm10	Atm^tm1Awb/Atm^tm1Awb	either: (A.129S6-Atm^tm1Awb x B6.129S6-Atm^tm1Awb)F1 or (B6.129S6-Atm^tm1Awb x A.129S6-Atm^tm1Awb)F1	MGI:5565480
hm11	Atm^tm1Awb/Atm^tm1Awb	involves: 129S6/SvEvTac	MGI:3761095
hm12	Atm^tm1Awb/Atm^tm1Awb	involves: 129S6/SvEvTac * C57BL/6	MGI:3615662
ht13	Atm^tm1Awb/Atm^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6	MGI:5614077
cx14	Atm^tm1Awb/Atm^tm1Awb Pim1^tm1Mjn/Pim1^+	involves: 129 * 129S6/SvEvTac * C57BL/6J	MGI:5491072
cx15	Atm^tm1Awb/Atm^tm1Awb Ppm1d^tm1Lad/Ppm1d^tm1Lad Tg(IghMyc)22Bri/0	involves: 129 * C57BL * FVB/N * SJL	MGI:3710183
cx16	Atm^tm1Awb/Atm^tm1Awb Rad52^tm1Aps/Rad52^tm1Aps	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3850721
cx17	Atm^tm1Awb/Atm^tm1Awb Cep63^Gt(EUCE0251h11)Hmgu/Cep63^Gt(EUCE0251h11)Hmgu	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:5819196
cx18	Atm^tm1Awb/Atm^tm1Awb Nbn^tm1Jpt/Nbn^tm1Jpt	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:3615888
cx19	Atm^tm1Awb/Atm^+ Rad50^tm2Jpt/Rad50^tm2Jpt	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:3615669
cx20	Atm^tm1Awb/Atm^tm1Awb Rad50^tm2Jpt/Rad50^tm2Jpt	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:3615663
cx21	Atm^tm1Awb/Atm^tm1Awb Nbn^tm2.1Jpt/Nbn^tm2.1Jpt	involves: 129S6/SvEvTac * 129/Sv	MGI:3771170
cx22	Atm^tm1Awb/Atm^tm1Awb Rad50^tm4.1Jpt/Rad50^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6	MGI:5614078
cx23	Atm^tm1Awb/Atm^tm1Awb Paxx^em1Spj/Paxx^em1Spj	involves: A/J * C57BL/6NTac	MGI:5829795

Genotype
MGI:5565477

hm1

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: 129S6/SvEvTac-Atm^tm1Awb

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

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

mortality/aging ( J:208539 )

N • Background Sensitivity: the number of homozygous pups produced from heterozygote matings on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio; fewer homozygous pups are produced on the C57BL/6 and A/J backgrounds

premature death ( J:208539 )

• median survival time is 113 days

• one mouse out of 40 survives to 18 months of age

• Background Sensitivity: survival time (least to most) on the following strain backgrounds is ranked as BALB/c < 129S6/SvEvTac < 129S6AF1 < 129S6B6F1 < C57BL/6 < A/J < B6AF1

neoplasm

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

Genotype
MGI:6110013

hm2

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: 129S6/SvEvTac-Atm^tm1Awb/J

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:226414 )

hematopoietic system

increased double-positive T cell number ( J:226414 )

• thymocytes exhibit an increase in the levels of immature CD4/CD8 double positive T-cells

increased B cell number ( J:226414 )

• increase in the percentage of B cells within the circulating lymphocyte populations at 2 months of age

decreased T cell number ( J:226414 )

• reduction in the percentage of T-cell subsets within the circulating lymphocyte population at 2 months of age

decreased single-positive T cell number ( J:226414 )

• thymocytes exhibit a decrease in the levels of more mature CD4 and CD8 single positive cells

immune system

increased double-positive T cell number ( J:226414 )

• thymocytes exhibit an increase in the levels of immature CD4/CD8 double positive T-cells

increased B cell number ( J:226414 )

• increase in the percentage of B cells within the circulating lymphocyte populations at 2 months of age

decreased T cell number ( J:226414 )

• reduction in the percentage of T-cell subsets within the circulating lymphocyte population at 2 months of age

decreased single-positive T cell number ( J:226414 )

• thymocytes exhibit a decrease in the levels of more mature CD4 and CD8 single positive cells

neoplasm

increased T cell derived lymphoma incidence ( J:226414 )

Genotype
MGI:5565476

hm3

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: A.129S6-Atm^tm1Awb

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

lethality, incomplete penetrance ( J:208539 )

• heterozygote x heterozygote matings produced fewer homozygotes than the expected Mendelian ratio

• Background Sensitivity: the number of homozygous pups produced from heterozygotes on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio

premature death ( J:208539 )

• Background Sensitivity: survival time (least to most) on the following strain backgrounds is ranked as BALB/c < 129S6/SvEvTac < 129S6AF1 < 129S6B6F1 < C57BL/6 < A/J < B6AF1

• median survival time is 385 days

• 4 mice out of 40 survive to 18 months of age

neoplasm

abnormal tumor susceptibility ( J:208539 )

• Background Sensitivity: mice are resistant to thymic lymphomas as compared to mice on the BALB/c, 129S6/SvEvTac, C57BL/6, B6AF1, 129S6B6F1, 129S6AF1 backgrounds

• 3 out of 40 mice develop thymic lymphomas by 18 months of age

increased hepatocellular carcinoma incidence ( J:208539 )

♂ • 4 out of 40 mice develop hepatocellular carcinomas as compared to 0 in wild type controls

♂ • tumors were only found in male mice

liver/biliary system

increased hepatocellular carcinoma incidence ( J:208539 )

♂ • 4 out of 40 mice develop hepatocellular carcinomas as compared to 0 in wild type controls

♂ • tumors were only found in male mice

Genotype
MGI:5829788

hm4

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: A.129S6-Atm^tm1Awb/J

mortality/aging

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

• following exposure to 5 Gy of whole-body gamma radiation, 2 of 2 mice (>12 weeks of age) die within 5 days post-treatment

homeostasis/metabolism

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

• following exposure to 5 Gy of whole-body gamma radiation, 2 of 2 mice (>12 weeks of age) die within 5 days post-treatment

Genotype
MGI:5565475

hm5

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: B6.129S6-Atm^tm1Awb

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

lethality, incomplete penetrance ( J:208539 )

• heterozygote x heterozygote matings produced fewer homozygotes than the expected Mendelian ratio

• Background Sensitivity: the number of homozygous pups produced from heterozygotes on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio

premature death ( J:208539 )

• median survival time is 353 days

• 8 mice out of 40 survive to 18 months of age

• Background Sensitivity: survival time (least to most) on the following strain backgrounds is ranked as BALB/c < 129S6/SvEvTac < 129S6AF1 < 129S6B6F1 < C57BL/6 < A/J < B6AF1

neoplasm

abnormal tumor incidence ( J:208539 )

• Background Sensitivity: mice are less susceptible to thymic lymphomas than on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 backgrounds

• 21 out of 40 mice die of thymic lymphomas

Genotype
MGI:5565474

hm6

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: CByJ.129S6-Atm^tm1Awb

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

mortality/aging ( J:208539 )

N • Background Sensitivity: the number of homozygous pups produced from heterozygote matings on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio; fewer homozygous pups are produced on the C57BL/6 and A/J backgrounds

premature death ( J:208539 )

• median survival time is 74 days, no mice survive beyond 109 days

• Background Sensitivity: survival time is shortest on this background as compared to the A/J, C57BL/6, 129S6B6F1, B6AF1 and 129S6AF1 backgrounds

neoplasm

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

Genotype
MGI:2175703

hm7

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: either: 129S6/SvEvTac-Atm^tm1Awb or (involves: 129S6/SvEvTac * NIH Black Swiss)

Oxidated stress in the brain of Atm^tm1Awb/Atm^tm1Awb mice indicated by increased levels of heme oxygenase

mortality/aging

increased mortality induced by gamma-irradiation ( J:34193 )

• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice

premature death ( J:34193 )

• many mice die from thymic lymphoma; none survived greater than 4.5 months of age without a thymic lymphoma

growth/size/body

decreased body size ( J:34193 )

• homozygotes appear smaller at birth

decreased body weight ( J:34193 )

• female and male homozygotes weigh less that control littermates from P8 to 3 months of age

immune system

immune system phenotype ( J:34193 )

N • no abnormalities in B lymphocytes, granulocytes or myeloid cells observed

increased double-positive T cell number ( J:34193 )

• increased number of immature double positive cells

decreased T cell number ( J:34193 )

• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes

decreased double-positive T cell number ( J:34193 )

• 59% reduction in Cd3/Cd4 double positive T lymphocytes

• 67% reduction in Cd3/Cd8 double positive T lymphocytes

• reduction in Cd5, Cd4, and Cd8 positive T lymphocytes

decreased activated T cell number ( J:34193 )

• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present

reproductive system

abnormal female reproductive system morphology ( J:34193 )

♀

absent ovarian follicles ( J:34193 )

♀ • absence of primordial and mature ovarian follicles

small ovary ( J:34193 )

♀

abnormal uterus morphology ( J:34193 )

♀ • no proliferation or degeneration in as part of the estrous cycle

abnormal gametogenesis ( J:34193 )

absent oocytes ( J:34193 )

♀ • complete absence of mature gametes

azoospermia ( J:34193 )

♂ • absence of mature sperm

arrest of spermatogenesis ( J:34193 )

♂

abnormal male reproductive system morphology ( J:34193 )

♂

abnormal seminiferous tubule morphology ( J:34193 )

♂ • reduced number of cells

♂ • degeneration of cells evident

♂ • some barren of all cells except Sertoli cells

small testis ( J:34193 )

♂

abnormal reproductive system physiology ( J:34193 )

absent estrus ( J:34193 )

♀ • females never enter estrous

absent estrous cycle ( J:34193 )

♀

female infertility ( J:34193 )

♀ • females never exhibit copulation plugs

male infertility ( J:34193 )

♂ • normal mating behavior evident by the presence of copulation plugs in control females; however, pregnancy never results

neoplasm

increased T cell derived lymphoma incidence ( J:34193 )

• thymic lymphomas are highly metastatic and consist of immature T cells

cellular

absent oocytes ( J:34193 )

♀ • complete absence of mature gametes

azoospermia ( J:34193 )

♂ • absence of mature sperm

abnormal lysosome morphology ( J:59933 )

• significant increase in the number of lysosomes in cerebellar Purkinje cells and in pyramidal cells of the hippocampus in the absence of any neuronal degeneration at 4-12 weeks of age, before the onset of T cell lymphoma

abnormal cell cycle ( J:34193 )

increased cellular sensitivity to gamma-irradiation ( J:34193 )

• mutant fibroblasts show increased radioresistant DNA synthesis (RDS) after 5 to 15 Gy of gamma-irradiation compared to controls, indicating that cell cycle checkpoints are abnormal

decreased fibroblast proliferation ( J:34193 )

• mutant fibroblasts grew more slowly in culture than control cells

oxidative stress ( J:57115 )

• tissues from mutants are under oxidative stress and suffer oxidative damage, especially in the brain

• oxidative damage to proteins and lipids as indicated by elevated nitrotyrosine levels in the brain (but not the liver) and elevated F2-isoprostanes in the testes (indicative of lipid damage)

• activity of the isozyme, heme oxygenase, is increased 600% in the cerebellum (but not in the cortex)

behavior/neurological

impaired coordination ( J:34193 )

• mutant mice were not able to stay on a rota-rod as long as controls

• impaired performance was not due to decreased strength since mice were able to suspend from a wire lid as long as controls

short stride length ( J:34193 )

• in addition, the maximum difference in stride lengths was greater in mutant mice, suggestive of ataxia

decreased vertical activity ( J:34193 )

• mutant mice reared less often than controls

decreased locomotor activity ( J:34193 )

• reduced horizontal activity was shown by reduced movement around an open field

nervous system

nervous system phenotype ( J:34193 )

N • no defects in brain architecture

N • no evidence of neurodegeneration

abnormal Purkinje cell morphology ( J:57115 )

• heme oxygenase 1 is increase in Purkinje cells, indicating oxidative damage particularly in these cells

hematopoietic system

increased double-positive T cell number ( J:34193 )

• increased number of immature double positive cells

decreased T cell number ( J:34193 )

• reduced number of mature single-positive Cd4+ and Cd8+ T lymphocytes

decreased double-positive T cell number ( J:34193 )

• 59% reduction in Cd3/Cd4 double positive T lymphocytes

• 67% reduction in Cd3/Cd8 double positive T lymphocytes

• reduction in Cd5, Cd4, and Cd8 positive T lymphocytes

decreased activated T cell number ( J:34193 )

• using Cd69 as a marker of activation, the number of Cd3/Cd69 or Cd8/Cd69 positive cells is reduced, but still present

endocrine/exocrine glands

absent ovarian follicles ( J:34193 )

♀ • absence of primordial and mature ovarian follicles

small ovary ( J:34193 )

♀

abnormal seminiferous tubule morphology ( J:34193 )

♂ • reduced number of cells

♂ • degeneration of cells evident

♂ • some barren of all cells except Sertoli cells

small testis ( J:34193 )

♂

increased T cell derived lymphoma incidence ( J:34193 )

• thymic lymphomas are highly metastatic and consist of immature T cells

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:34193 )

• mutant mice die from radiation induced toxicity to the gastrointestinal tract at doses that do not kill control mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ataxia telangiectasia		DOID:12704	OMIM:208900	J:34193 , J:57115

Genotype
MGI:5565479

hm8

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: either: (129S6/SvEvTac-Atm^tm1Awb x A.129S6-Atm^tm1Awb)F1 or (A.129S6-Atm^tm1Awb x 129S6/SvEvTac-Atm^tm1Awb)F1

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

mortality/aging ( J:208539 )

N • Background Sensitivity: the number of homozygous pups produced from heterozygote matings on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio; fewer homozygous pups are produced on the C57BL/6 and A/J backgrounds

premature death ( J:208539 )

• median survival time is 139 days

• 4 mice out of 39 survive to 18 months of age

• Background Sensitivity: survival time (least to most) on the following strain backgrounds is ranked as BALB/c < 129S6/SvEvTac < 129S6AF1 < 129S6B6F1 < C57BL/6 < A/J < B6AF1

neoplasm

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

Genotype
MGI:5565478

hm9

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: either: (129S6/SvEvTac-Atm^tm1Awb x B6.129S6-Atm^tm1Awb)F1 or (B6.129S6-Atm^tm1Awb x 129S6/SvEvTac-Atm^tm1Awb)F1

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

mortality/aging ( J:208539 )

N • Background Sensitivity: the number of homozygous pups produced from heterozygote matings on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio; fewer homozygous pups are produced on the C57BL/6 and A/J backgrounds

premature death ( J:208539 )

• median survival time is 200 days

• 5 mice out of 39 survive to 18 months of age

• Background Sensitivity: survival time (least to most) on the following strain backgrounds is ranked as BALB/c < 129S6/SvEvTac < 129S6AF1 < 129S6B6F1 < C57BL/6 < A/J < B6AF1

neoplasm

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:208539 )

• almost all mice die of thymic lymphomas

• Background Sensitivity: mice have a higher thymic lymphoma incidence than do homozygous Atm^tm1Awb mice on the C57BL/6, B6AF1 and A/J backgrounds

Genotype
MGI:5565480

hm10

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: either: (A.129S6-Atm^tm1Awb x B6.129S6-Atm^tm1Awb)F1 or (B6.129S6-Atm^tm1Awb x A.129S6-Atm^tm1Awb)F1

growth/size/body

decreased body weight ( J:208539 )

• pups of the same sex measured weekly from 5-12 weeks of age weigh less than wild type controls at all time points

mortality/aging

mortality/aging ( J:208539 )

N • Background Sensitivity: the number of homozygous pups produced from heterozygote matings on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 and B6AF1 backgrounds reaches the expected Mendelian ratio; fewer homozygous pups are produced on the C57BL/6 and A/J backgrounds

premature death ( J:208539 )

• median survival time is 451 days

• 6 mice out of 39 survive to 18 months of age

• Background Sensitivity: survival time is longest on this background as compared to A/J, BALB/c, 129S6/SvEvTac, C57BL/6, 129S6B6F1 and 129S6AF1 backgrounds

neoplasm

abnormal tumor incidence ( J:208539 )

• Background Sensitivity: mice are less susceptible to thymic lymphomas than on the BALB/c, 129S6/SvEvTac, 129S6B6F1, 129S6AF1 backgrounds

• 5 out of 20 males and 13 out of 20 mice die of thymic lymphomas

Genotype
MGI:3761095

hm11

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: involves: 129S6/SvEvTac

mortality/aging

increased mortality induced by gamma-irradiation ( J:90941 )

premature death ( J:90941 )

• median survival is 16 weeks

immune system

immune system phenotype ( J:126920 )

N • thymic apoptosis following exposure to radiation is normal

abnormal class switch recombination ( J:150435 )

• B cells have about a 5-fold reduction in class switch recombination to IgG1

• there is small increase in switch junctions showing three or more nucleotide insertions

decreased CD4-positive, alpha-beta T cell number ( J:90941 )

• in thymus and spleen

decreased CD8-positive, alpha-beta T cell number ( J:90941 )

• in thymus and spleen

cellular

cellular phenotype ( J:126186 )

N • mouse embryonic fibroblast cells arrest and undergo apoptosis following exposure to ionizing radiation

abnormal chromosome morphology ( J:170462 )

• lymphoma cells show Chromosome 14 translocations at the TCR alpha/delta locus

• DNA losses in distal Chromosome 12 near the Igh locus

abnormal cell cycle checkpoint function ( J:126920 )

• mouse embryonic fibroblasts exposed to radiation fail to arrest at the G1/S transition unlike similarly treated wild-type cells

spontaneous chromosome breakage ( J:150435 )

• 10%-20% of B cells harbored IgH-specific breaks, 0.5%-3.5% carried IgH translocations, and 20%-30% had non-IgH associated instability

• incubation with DNA-PKcs kinase inhibitors dramatically increases genomic instability and almost doubles the frequency of myc/IgH translocations

growth/size/body

decreased body weight ( J:90941 )

• 25%

hematopoietic system

abnormal class switch recombination ( J:150435 )

• B cells have about a 5-fold reduction in class switch recombination to IgG1

• there is small increase in switch junctions showing three or more nucleotide insertions

decreased CD4-positive, alpha-beta T cell number ( J:90941 )

• in thymus and spleen

decreased CD8-positive, alpha-beta T cell number ( J:90941 )

• in thymus and spleen

neoplasm

increased T cell derived lymphoma incidence ( J:90941 )

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:90941 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:90941 )

Genotype
MGI:3615662

hm12

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:103922 )

• majority die with thymic lymphomas by 5 months of age, 2.9% live up to 10 months, and none live beyond 15 months

neoplasm

increased T cell derived lymphoma incidence ( J:103922 )

• majority die with thymic lymphomas

cellular

abnormal cell cycle checkpoint function ( J:103922 )

• MEFs exhibit defects in G1/S, intra-S-phase, and G2/M checkpoints after ionizing radiation induced DNA damage

chromosome breakage ( J:103922 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:103922 )

• majority die with thymic lymphomas

Genotype
MGI:5614077

ht13

• Allelic Composition: Atm^tm1Awb/Atm⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6

reproductive system

abnormal seminiferous tubule morphology ( J:209141 )

• cellularity is increased compared to mutant mice wild-type for Atm

abnormal testis size ( J:209141 )

• 2-fold larger than in mutant mice wild-type for Atm

hematopoietic system

hematopoietic system phenotype ( J:209141 )

N • unlike mutant mice wild-type for Atm, the LSK population is similar to wild-type controls

nervous system

nervous system phenotype ( J:209141 )

N • unlike mutant mice wild-type for Atm, no mice with hydrocephaly are seen

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:209141 )

• cellularity is increased compared to mutant mice wild-type for Atm

abnormal testis size ( J:209141 )

• 2-fold larger than in mutant mice wild-type for Atm

Genotype
MGI:5491072

cx14

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Pim1^tm1Mjn/Pim1⁺
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6J

cellular

cellular phenotype ( J:194229 )

N • no defect in homology directed repair is detected in MEFs or ear fibroblasts

Genotype
MGI:3710183

cx15

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Ppm1d^tm1Lad/Ppm1d^tm1Lad; Tg(IghMyc)22Bri/0
• Genetic Background: involves: 129 * C57BL * FVB/N * SJL

mortality/aging

premature death ( J:120284 )

• the median lifespan of 69 days

neoplasm

increased tumor incidence ( J:120284 )

• based on median survival time, mice carrying double Atm^tm1Awb allele were no more resistant to tumor formation induced by myc than mice with homozygous wild-type Ppm1d⁺ allele

Genotype
MGI:3850721

cx16

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Rad52^tm1Aps/Rad52^tm1Aps
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

increased mortality induced by gamma-irradiation ( J:90941 )

premature death ( J:90941 )

• median survival is 33 weeks compared to 16 weeks for Atm^tm1Awb homozygotes

neoplasm

increased T cell derived lymphoma incidence ( J:90941 )

• mice develop thymic tumors

decreased lymphoma incidence ( J:90941 )

• unlike in Atm^tm1Awb homozygotes, mice rarely develop T cell lymphomas

immune system

decreased CD4-positive, alpha-beta T cell number ( J:90941 )

• in thymus

decreased CD8-positive, alpha-beta T cell number ( J:90941 )

• in thymus

growth/size/body

decreased body weight ( J:90941 )

• 25%

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:90941 )

• in thymus

decreased CD8-positive, alpha-beta T cell number ( J:90941 )

• in thymus

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:90941 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:90941 )

• mice develop thymic tumors

Genotype
MGI:5819196

cx17

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Cep63^{Gt(EUCE0251h11)Hmgu}/Cep63^{Gt(EUCE0251h11)Hmgu}
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

nervous system

thin cerebral cortex ( J:224364 )

• significant reduction in cortical thickness, as determined in motor and visual cortex sections at P60, similar to that in single Cep63^{Gt(EUCE0251h11)Hmgu} homozygotes

Genotype
MGI:3615888

cx18

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Nbn^tm1Jpt/Nbn^tm1Jpt
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

mortality/aging

embryonic lethality, complete penetrance ( J:75956 )

• no embryos detected at E10, stage of death not determined

Genotype
MGI:3615669

cx19

• Allelic Composition: Atm^tm1Awb/Atm⁺; Rad50^tm2Jpt/Rad50^tm2Jpt
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:103922 )

• although most succumb to anemia, they have a significantly greater survival time than homozygous Rad50^tm2Jpt mice, with 85% living longer than 5 months of age

neoplasm

increased lymphoma incidence ( J:103922 )

• 16 of 67 develop lymphoma

hematopoietic system

anemia ( J:103922 )

• most succumb to anemia

decreased macrophage cell number ( J:103922 )

• macrophage counts are decreased to a similar level as in homozygous Atm^tm1Awb mice

immune system

decreased macrophage cell number ( J:103922 )

• macrophage counts are decreased to a similar level as in homozygous Atm^tm1Awb mice

Genotype
MGI:3615663

cx20

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Rad50^tm2Jpt/Rad50^tm2Jpt
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:103922 )

• although die of malignancy, they have a significantly greater survival time than homozygous Rad50^tm2Jpt mice, with 42% living longer than 5 months, 20.5% surviving to 10 months and 18% surviving to 15 months

neoplasm

increased lymphoma incidence ( J:103922 )

• although mutants develop lymphomas, the latency of lymphomagenesis is increased compared to homozygous Atm^tm1Awb mice

cellular

cellular phenotype ( J:103922 )

N • growth of MEFs and sensitivity to irradiation is comparable to wild-type indicating rescue of the slower growth of MEFs and increased sensitivity to gamma-irradiation that is seen in homozygous Atm^tm1Awb mice

abnormal cell cycle checkpoint function ( J:103922 )

• MEFs exhibit defects in G1/S, intra-S-phase, and G2/M checkpoints after ionizing radiation induced DNA damage

chromosome breakage ( J:103922 )

• exhibit some chromosomal instability, however it is slightly reduced relative to homozygous Atm mice

hematopoietic system

anemia ( J:103922 )

• 4 of 42 develop anemia

Genotype
MGI:3771170

cx21

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Nbn^tm2.1Jpt/Nbn^tm2.1Jpt
• Genetic Background: involves: 129S6/SvEvTac * 129/Sv

cellular

decreased cellular sensitivity to ionizing radiation ( J:129762 )

• cells undergo fail to exhibit increased levels of apoptosis following exposure to ionizing radiation

Genotype
MGI:5614078

cx22

• Allelic Composition: Atm^tm1Awb/Atm^tm1Awb; Rad50^tm4.1Jpt/Rad50⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6

neoplasm

increased tumor latency ( J:209141 )

• marked increase in the latency of thymic lymphomas compared to mutant mice wild-type for Rad50

Genotype
MGI:5829795

cx23

• 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