Phenotypes associated with this allele

• Allele Symbol: Atr^tm2Bal
• Allele Name: targeted mutation 2, David Baltimore
• Allele ID: MGI:2656567
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Atr^tm2Bal/Atr^tm2Bal Cdkn2a^tm2Brn/Cdkn2a^tm2Brn Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:5316228
cn2	Atr^tm1Bal/Atr^tm2Bal Ndor1^Tg(UBC-cre/ERT2)1Ejb/0	involves: 129S/SvEv * 129S2/SvPas * C57BL/6	MGI:3717476
cn3	Atr^tm1Bal/Atr^tm2Bal Tg(Syn1-cre)671Jxm/0	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CBA	MGI:3717477
cn4	Atr^tm2Bal/Atr^tm2Bal Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:5316225
cn5	Atr^tm2Bal/Atr^tm2Bal Tg(Nes-cre)1Kln/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:5316221
cn6	Atr^tm2Bal/Atr^tm2Bal Trp53^tm1Tyj/Trp53^tm1Tyj Tg(Nes-cre)1Kln/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:5316227
cn7	Atm^tm2Pmc/Atm^tm2Pmc Atr^tm2Bal/Atr^tm2Bal Tg(Nes-cre)1Kln/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:5316230
cn8	Atr^tm2Bal/Atr^tm2Bal Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:5316224

Genotype
MGI:5316228

cn1

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Cdkn2a^tm2Brn/Cdkn2a^tm2Brn; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

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

nervous system

abnormal nervous system morphology ( J:181920 )

• similar neuropathology to mutant mice wild-type for Cdkn2a

Genotype
MGI:3717476

cn2

• Allelic Composition: Atr^tm1Bal/Atr^tm2Bal; Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/0
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6

growth/size/body

decreased body weight ( J:123200 )

• 1 year after tamoxifen treatment, treated mice show a 20% decrease in body weigh compared to controls (21.3 g vs 26.6 g in controls)

pigmentation

abnormal coat/hair pigmentation ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, within 3-4 months pervasive graying of the coat is observed; no obvious phenotype is observed in controls

skeleton

kyphosis ( J:123200 )

• between 3 and 12 months after tamoxifen treatment, mice show significant kyphosis relative to control mice

decreased compact bone thickness ( J:123200 )

• 1 year after tamoxifen treatment, mice show an 18% decrease in cortical bone cross-sectional area as determined by micro-CT

abnormal trabecular bone morphology ( J:123200 )

• 1 year after tamoxifen treatment, mice show a 46-76% reduction in trabecular bone volume as determined by micro-CT

osteoporosis ( J:123200 )

• after tamoxifen treatment, mice begin to develop osteoporosis

endocrine/exocrine glands

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

sebaceous gland hyperplasia ( J:123200 )

• hair follicles often display sebaceous gland cell hyperplasia

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

hematopoietic system

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

immune system

decreased thymocyte number ( J:123200 )

• by 1-2 weeks after tamoxifen treatment, relative to controls, mice show marked suppression of thymocyte numbers which recover by 3-4 months after treatment; 6-7 months after treatment, numbers are significantly decreased again relative to controls

abnormal thymus involution ( J:123200 )

• mice display premature thymic involution (~1 year) after tamoxifen treatment

kidney inflammation ( J:123200 )

• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment

liver/biliary system

abnormal liver morphology ( J:123200 )

• a significant increase in senescence-associated betagalactosidase-positive cells is observed in the liver 1 year after tamoxifen treatment

renal/urinary system

kidney inflammation ( J:123200 )

• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment

kidney atrophy ( J:123200 )

• by 1 year after tamoxifen treatment, kidneys display atrophy

renal glomerulus atrophy ( J:123200 )

• glomerular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment, but not in controls

renal tubule atrophy ( J:123200 )

• tubular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment

renal fibrosis ( J:123200 )

• fibrotic tissue accumulates in kidneys of tamoxifen-treated mice with age

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:123200 )

• 1 week after tamoxifen treatment, ~80% of villus epithelium is lost, but recovers fully by 1 months after treatment

cardiovascular system

cardiac fibrosis ( J:123200 )

• compared to control mice, fibrotic tissue accumulates in hearts of tamoxifen-treated mice with age

adipose tissue

decreased subcutaneous adipose tissue amount ( J:123200 )

• layer is reduced up to 70% in thickness 3-6 months after tamoxifen treatment

cellular

decreased cell proliferation ( J:123200 )

• temporary loss of proliferating cells after tamoxifen treatment is observed in intestine, skin, kidney and liver

integument

decreased subcutaneous adipose tissue amount ( J:123200 )

• layer is reduced up to 70% in thickness 3-6 months after tamoxifen treatment

sebaceous gland hyperplasia ( J:123200 )

• hair follicles often display sebaceous gland cell hyperplasia

abnormal coat/hair pigmentation ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, within 3-4 months pervasive graying of the coat is observed; no obvious phenotype is observed in controls

abnormal hair growth ( J:123200 )

• after a third round of depilation, hair regrowth does not occur or regrows predominantly gray

alopecia ( J:123200 )

• when mice are treated with tamoxifen at 8-12 weeks of age, a progressive alopecia develops within 3-4 months, increasing in expressivity past 1 year of age

• single topical doses of 4-hydroxytamoxifen to skin causes alopecia and gray hair regrowth

abnormal hair shaft morphology ( J:123200 )

• remaining follicles in mice >6 months display gray shafts

• after depilation in tamoxifen-treated mice, hair shaft generation is delayed and compromised in abundance and quality

abnormal hair follicle morphology ( J:123200 )

• remaining hair follicles often show abnormal architecture with degeneration of dermal and epidermal structures

abnormal hair follicle development ( J:123200 )

• significantly delayed after tamoxifen treatment

• development is delayed in anagen after tamoxifen treatment

decreased hair follicle number ( J:123200 )

• loss of hair follicles is observed 3-6 months after tamoxifen treatment

abnormal hair cycle ( J:123200 )

• following depilation in tamoxifen-treated mice, anagen phase is accompanied by widespread degenerative follicles 4 days after depilation and delay in anagen progression 8 days after depilation

• after a second round of depilation in telogen phase, hair regrowth is more sparse, with increased representation of gray hair shafts

delayed hair regrowth ( J:123200 )

• after a second round of depilation in telogen phase, hair regrowth is more sparse, with increased representation of gray hair shafts

thick skin ( J:123200 )

• mice develop thickened epidermis 3-6 months after tamoxifen treatment

Genotype
MGI:3717477

cn3

• Allelic Composition: Atr^tm1Bal/Atr^tm2Bal; Tg(Syn1-cre)671Jxm/0
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CBA

behavior/neurological

behavior/neurological phenotype ( J:123200 )

N • tamoxifen-treated mice do not show any significant differences from controls in circadian activity, strength, motor coordination, anxiety-like behavior, learning or memory

Genotype
MGI:5316225

cn4

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

cellular

abnormal neuron proliferation ( J:181920 )

• decrease in proliferation in cultured neurospheres after 4OHT treatment

nervous system

abnormal neuron proliferation ( J:181920 )

• decrease in proliferation in cultured neurospheres after 4OHT treatment

Genotype
MGI:5316221

cn5

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:181920 )

• die by P7

nervous system

increased neuron apoptosis ( J:181920 )

• elevated apoptosis is detected in the external granule cell layer at E16.5

• high levels of DNA damage and elevated apoptosis in the ganglionic eminence at E15.5

abnormal neuron proliferation ( J:181920 )

• striking decrease in proliferation at E16.5 in the rhombic lip

• decrease in the size and growth of neurospheres indicating a defect in proliferation

decreased cerebellar granule cell precursor proliferation ( J:181920 )

• striking decrease in proliferation at E16.5 in the cerebellar external granule cell layer

abnormal cerebellum development ( J:181920 )

• marked defects in cerebellar development

abnormal rhombic lip morphology ( J:181920 )

• striking decrease in proliferation at E16.5 in the rhombic lip

decreased brain size ( J:181920 )

abnormal corpus callosum morphology ( J:181920 )

• decreased cellularity

abnormal cerebral cortex morphology ( J:181920 )

• decreased cellularity, especially in the upper layers

abnormal olfactory bulb granule cell layer morphology ( J:181920 )

• depleted

ectopic Purkinje cell ( J:181920 )

• mislocalization of Purkinje cells

abnormal cerebellar granule layer morphology ( J:181920 )

• defects in foliation and mislocalization of Purkinje cells

decreased cerebellar granule cell number ( J:181920 )

abnormal embryonic/fetal subventricular zone morphology ( J:181920 )

• high levels of DNA damage and elevated apoptosis in the ganglionic eminence at E15.5

growth/size/body

decreased body size ( J:181920 )

postnatal growth retardation ( J:181920 )

cellular

increased neuron apoptosis ( J:181920 )

• elevated apoptosis is detected in the external granule cell layer at E16.5

• high levels of DNA damage and elevated apoptosis in the ganglionic eminence at E15.5

abnormal neuron proliferation ( J:181920 )

• striking decrease in proliferation at E16.5 in the rhombic lip

• decrease in the size and growth of neurospheres indicating a defect in proliferation

decreased cerebellar granule cell precursor proliferation ( J:181920 )

• striking decrease in proliferation at E16.5 in the cerebellar external granule cell layer

Genotype
MGI:5316227

cn6

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Trp53^tm1Tyj/Trp53^tm1Tyj; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

nervous system

abnormal neuron apoptosis ( J:181920 )

• attenuated apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Trp53

• partial rescue of apoptosis in the forebrain compared to mutant mice wild-type for Trp53

abnormal neuron proliferation ( J:181920 )

• substantial enhancement of neurosphere size and growth compared to mutant mice wild-type for Trp53

• however, after 7 days in culture expansion stops and cells fail to survive

abnormal nervous system morphology ( J:181920 )

• similar neuropathology to mutant mice wild-type for Trp53

cellular

abnormal neuron apoptosis ( J:181920 )

• attenuated apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Trp53

• partial rescue of apoptosis in the forebrain compared to mutant mice wild-type for Trp53

abnormal neuron proliferation ( J:181920 )

• substantial enhancement of neurosphere size and growth compared to mutant mice wild-type for Trp53

• however, after 7 days in culture expansion stops and cells fail to survive

Genotype
MGI:5316230

cn7

• Allelic Composition: Atm^tm2Pmc/Atm^tm2Pmc; Atr^tm2Bal/Atr^tm2Bal; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

nervous system

abnormal neuron apoptosis ( J:181920 )

• decrease in apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Atm

abnormal nervous system morphology ( J:181920 )

• similar neuropathology to mutant mice wild-type for Atm

cellular

decreased cellular sensitivity to ionizing radiation ( J:181920 )

• resistance to radiation induced DNA damage-induced apoptosis in neural tissues

abnormal neuron apoptosis ( J:181920 )

• decrease in apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Atm

Genotype
MGI:5316224

cn8

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

nervous system

abnormal corpus callosum morphology ( J:181920 )

• decreased in size and cellularity

hippocampus hypoplasia ( J:181920 )

• reduced cellularity

abnormal cerebral cortex morphology ( J:181920 )

• moderate perturbation of cortical development

• reduced cellularity, particularly in layers IV-II

abnormal stratification in cerebral cortex ( J:181920 )

• decrease in layer demarcation, particularly in layers IV-II