Phenotypes Associated with This Genotype

Genotype
MGI:3717476

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

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

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