Mouse Genome Informatics
cn1
    Atrtm2Bal/Atrtm2Bal
Cdkn2atm2Brn/Cdkn2atm2Brn
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• similar neuropathology to mutant mice wild-type for Cdkn2a


Mouse Genome Informatics
cn2
    Atrtm1Bal/Atrtm2Bal
Tg(UBC-cre/ERT2)1Ejb/0

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• 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
• 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
• between 3 and 12 months after tamoxifen treatment, mice show significant kyphosis relative to control mice
• 1 year after tamoxifen treatment, mice show an 18% decrease in cortical bone cross-sectional area as determined by micro-CT
• 1 year after tamoxifen treatment, mice show a 46-76% reduction in trabecular bone volume as determined by micro-CT
• after tamoxifen treatment, mice begin to develop osteoporosis

endocrine/exocrine glands
• hair follicles often display sebaceous gland cell hyperplasia
• 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
• mice display premature thymic involution (~1 year) after tamoxifen treatment

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

immune system
• 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
• mice display premature thymic involution (~1 year) after tamoxifen treatment
• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment

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

renal/urinary system
• leukocyte infiltration of the kidneys is observed in all tamoxifen-treated mice at 1 year post-treatment
• by 1 year after tamoxifen treatment, kidneys display atrophy
• glomerular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment, but not in controls
• tubular degeneration in all kidneys of tamoxifen-treated mice at 1 year after treatment
• fibrotic tissue accumulates in kidneys of tamoxifen-treated mice with age

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

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

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

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

integument
• layer is reduced up to 70% in thickness 3-6 months after tamoxifen treatment
• hair follicles often display sebaceous gland cell hyperplasia
• 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
• after a third round of depilation, hair regrowth does not occur or regrows predominantly gray
• 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
• 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
• remaining hair follicles often show abnormal architecture with degeneration of dermal and epidermal structures
• significantly delayed after tamoxifen treatment
• development is delayed in anagen after tamoxifen treatment
• loss of hair follicles is observed 3-6 months after tamoxifen treatment
• 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
• after a second round of depilation in telogen phase, hair regrowth is more sparse, with increased representation of gray hair shafts
• mice develop thickened epidermis 3-6 months after tamoxifen treatment


Mouse Genome Informatics
cn3
    Atrtm1Bal/Atrtm2Bal
Tg(Syn1-cre)671Jxm/0

involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• tamoxifen-treated mice do not show any significant differences from controls in circadian activity, strength, motor coordination, anxiety-like behavior, learning or memory (J:123200)


Mouse Genome Informatics
cn4
    Atrtm2Bal/Atrtm2Bal
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• decrease in proliferation in cultured neurospheres after 4OHT treatment

nervous system
• decrease in proliferation in cultured neurospheres after 4OHT treatment


Mouse Genome Informatics
cn5
    Atrtm2Bal/Atrtm2Bal
Tg(Nes-cre)1Kln/0

involves: 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• 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
• striking decrease in proliferation at E16.5 in the rhombic lip
• decrease in the size and growth of neurospheres indicating a defect in proliferation
• striking decrease in proliferation at E16.5 in the cerebellar external granule cell layer
• marked defects in cerebellar development
• striking decrease in proliferation at E16.5 in the rhombic lip
• decreased cellularity
• decreased cellularity, especially in the upper layers
• mislocalization of Purkinje cells
• defects in foliation and mislocalization of Purkinje cells
• high levels of DNA damage and elevated apoptosis in the ganglionic eminence at E15.5

growth/size

cellular
• 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
• striking decrease in proliferation at E16.5 in the rhombic lip
• decrease in the size and growth of neurospheres indicating a defect in proliferation
• striking decrease in proliferation at E16.5 in the cerebellar external granule cell layer


Mouse Genome Informatics
cn6
    Atrtm2Bal/Atrtm2Bal
Trp53tm1Tyj/Trp53tm1Tyj
Tg(Nes-cre)1Kln/0

involves: 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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
• similar neuropathology to mutant mice wild-type for Trp53

cellular
• 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
• 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


Mouse Genome Informatics
cn7
    Atmtm2Pmc/Atmtm2Pmc
Atrtm2Bal/Atrtm2Bal
Tg(Nes-cre)1Kln/0

involves: 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• decrease in apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Atm
• similar neuropathology to mutant mice wild-type for Atm

cellular
• decrease in apoptosis in the external granule layer and ganglionic eminence compared to mutant mice wild-type for Atm
• resistance to radiation induced DNA damage-induced apoptosis in neural tissues


Mouse Genome Informatics
cn8
    Atrtm2Bal/Atrtm2Bal
Emx1tm1(cre)Krj/Emx1+

involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• decreased in size and cellularity
• reduced cellularity
• moderate perturbation of cortical development
• reduced cellularity, particularly in layers IV-II
• decrease in layer demarcation, particularly in layers IV-II