Mouse Genome Informatics
cn1
    Rtn4rtm2.1Stmr/Rtn4rtm2.2Stmr
Tg(CAG-cre/Esr1*)5Amc/0

B6.Cg-Rtn4rtm2.1Stmr/Rtn4rtm2.2Stmr Tg(CAG-cre/Esr1*)5Amc0
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• after optic nerve crush, tamoxifen-treated mice exhibit stronger axonal regeneration compared with control mice though not as complete as in constitutive knock-out mice
• after spinal cord dorsal hemisection injury, tamoxifen-treated mice exhibit improvement of motor function and 5HT fiber density compared with control mice
• however, untreated mice exhibit normal regeneration


Mouse Genome Informatics
cn2
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sortm7(SMO*/YFP)Amc
Tg(CAG-cre/Esr1*)5Amc/0

chimera involves: 129S4/SvJae *129X1/SvJ * C57BL/6 * CBA * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dorsal CNS hyperproliferation at E13.5 after being exposed at E8.5 to tamoxifen

limbs/digits/tail
• observed at E13.5 after being exposed at E8.5 to tamoxifen


Mouse Genome Informatics
cn3
    Gnl3tm2.1Rylt/Gnl3tm2.1Rylt
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * 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
• increase in the percentage of MEFs showing signs of replication-induced DNA damage after tamoxifen treatment
• tamoxifen treatment impairs the long-term proliferative potential of MEFs


Mouse Genome Informatics
cn4
    Gnl3tm2.1Rylt/Gnl3tm2.1Rylt
Trp53tm1Tyj/Trp53tm1Tyj
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * 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
• increase in the percentage of MEFs showing signs of replication-induced DNA damage after tamoxifen treatment
• tamoxifen treatment shortens the lifespan of MEFs
• tamoxifen treatment impairs the long-term proliferative potential of MEFs


Mouse Genome Informatics
cn5
    Tbx3tm3.1Moon/Tbx3tm3.1Moon
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• in tamoxifen-treated mice
• second degree in tamoxifen-treated mice


Mouse Genome Informatics
cn6
    Mecomtm1Aspe/Mecomtm2.1Aspe
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• tamoxifen-treated mice lack long-term repopulating cells (or high proliferative potential colony-forming cells; HPP-CFC) unlike wild-type mice
• granulocyte and macrophage progenitors (CFU-G and CFU-M, respectively) are increase compared with wild-type mice
• tamoxifen-treated mice exhibit fewer multipotent progenitors (CFU-GEMM) and granulocyte-macrophage progenitor (CFU-GM) compared with wild-type mice


Mouse Genome Informatics
cn7
    Sox4tm1Vlf/Sox4tm1Vlf
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• when treated with tamoxifen, mice die between E13.5 and E14.5 likely due to regurgitation of blood into the heart

cardiovascular system
• when treated with tamoxifen
• at E13.5, mice exhibit incomplete septation of the ventricles when treated with tamoxifen
• endocardial cushions form at the level of the semilunar valve but functional flaps do not form when treated with tamoxifen

homeostasis/metabolism
• at E13.5 when treated with tamoxifen


Mouse Genome Informatics
cn8
    Pax3tm1.1Sjc/Pax3tm1.1Sjc
Pax7tm1.2Fan/Pax7tm1.2Fan
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• following tamoxifen-treatment, muscle regeneration is normal as are the proliferative and myogenic properties of adult myoblasts (J:150962)


Mouse Genome Informatics
cn9
    Tardbptm1.1Pcw/Tardbp+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• after cre induction by tamoxifen, mice show decrease in body weight relative to controls

adipose tissue
• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected
• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected


Mouse Genome Informatics
cn10
    Tardbptm1.1Pcw/Tardbptm1.1Pcw
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129 * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
• after cre induction by tamoxifen, mice show decrease in body relative to controls

cellular
• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes

adipose tissue
• inspection of animals dying after cre induction by tamoxifen shows loss of body fat in these mice
• analyses of carcasses show significant decreases in whole body fat mass, but not lean mass
• absence of fatty acid vacuoles in adipocytes in interscapular brown fat is detected
• adipocytes are present in brown fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen
• dramatic fat loss is observed
• reduction of fatty acid vacuoles in adipocytes in subcutaneous fat is detected
• adipocytes are present in white fat, but lack of stored fat within adipocytes results in loss of fat content in animals after induction by tamoxifen

homeostasis/metabolism
• increased fat oxidation after loss of Tardbp results in fat loss in adipocytes


Mouse Genome Informatics
cn11
    Tg(CAG-Bgeo/Lhx2,-GFP)#Lcar/0
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• areas of skin that are tamoxifen treated prematurely initiated anagen and are in anagen at 9 weeks of age, whereas in wild-type mice and untreated areas of skin are in telogen.


Mouse Genome Informatics
cn12
    Tg(CAG-cre/Esr1*)5Amc/?
Thratm1Ffla/Thra+

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thratm1Ffla Tg(Sycp1-cre)4Min mice

growth/size
• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thratm1Ffla Tg(Sycp1-cre)4Min mice

cardiovascular system
• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thratm1Ffla Tg(Sycp1-cre)4Min mice

skeleton
• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thratm1Ffla Tg(Sycp1-cre)4Min mice


Mouse Genome Informatics
cn13
    Nlrp3tm1Hhf/Nlrp3+
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro
• bone marrow derived dendritic cells hypersecrete the mature form of IL-1beta in response to activation
• the maximal response is 300-fold greater than controls
• DCs are able to secrete IL1-beta without the presence of exogenous ATP
• mutant DCs cells have an enhanced ability to stimulate T cells to differentiate into a Th17 subtypes when presenting cognate antigen
• mutant DCs also enhance Th1 and Th2 differentation when co-cultured with T cells in the presence of polarizing cytokines

hematopoietic system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150054


Mouse Genome Informatics
cn14
    Nlrp3tm2Hhf/Nlrp3+
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro
• bone marrow derived dendritic cells (DCs) spontaneously secrete high levels of IL1-beta in response to cold (32 degrees) incubation
• DCs also hypersecrete the mature form of IL-1beta in response to activation
• the maximal response is 150-fold greater than controls
• DCs are able to secrete IL1-beta without the presence of exogenous ATP

hematopoietic system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

Mouse Models of Human Disease
OMIM IDRef(s)
Familial Cold Autoinflammatory Syndrome 1; FCAS1 120100 J:150054


Mouse Genome Informatics
cn15
    Gfra1tm1Jmi/Gfra1tm2Jmi
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129/Sv * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• with 4-OHT treatment on E13.5 rather than E15.5, complete loss of enteric neurons in colon is still observed at E18.5, but no abnormalities in enteric ganglia of small intestine is seen (J:122607)
• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)
• at E18.5, ganglion structure and innervation in the colon is completely disrupted relative to control mice with 4-OHT treatement at E15.5
• enteric ganglion cells die within 36 hours after 4-OHT treatment
• with 4-OHT treatment on E15.5, enteric ganglia and neurons are lost in the colon by birth
• abnormal thick nerve bundles are observed in the colons of E18.5 embryos after 4-hydroxytamoxifen, 4-OHT treatment on E15.5; this are likely un-defasciculated extrinsic nerve fibers

cellular
• nuclei of dying ganglion cells in mutants display numerous indentations in nuclear membrane, some with abnormal constriction of the nuclear membrane resulting in multilobation of the nuclei
• cells are shrunken with condensation of marginal heterochromatin and chromatin masses dispersed in the karyoplasms; diminuition of the cytoplasm and heterochromatin condensation in the nuclei are enhanced in ganglion cells in the myenteric layer
• enteric ganglion cells die within 36 hours of Gfra1 inactivation induced by 4-OHT treatment of pregnant females, but cell death is by mechanism other than apoptosis; enteric neuron death is not dependent on caspases or Bax
• some cells contain autolysosomes; almost no autophagosomes are detected in mutants at any stage of cell death
• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)


Mouse Genome Informatics
cn16
    Foxn1tm1.1Dmsu/Foxn1tm1.1Dmsu
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129/Sv * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Thymic atrophy in tamoxifen treated Foxn1tm1.1Dmsu/Foxn1tm1.1Dmsu Tg(KRT5-cre/ERT2)2Ipc/0 mice and Foxn1tm1.1Dmsu/Foxn1tm1.1Dmsu Tg(CAG-cre/Esr1*)5Amc/0 mice

immune system
• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice
• following tamoxifen treatment
• following tamoxifen treatment
• following tamoxifen treatment
• following tamoxifen treatment

hematopoietic system
• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice
• following tamoxifen treatment
• following tamoxifen treatment
• following tamoxifen treatment
• following tamoxifen treatment

endocrine/exocrine glands
• following tamoxifen treatment, mice exhibit a decrease in thymic stromal cells compared to in wild-type mice
• following tamoxifen treatment
• following tamoxifen treatment
• following tamoxifen treatment


Mouse Genome Informatics
cn17
    Foxn1nu/Foxn1tm1.1Dmsu
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129/Sv * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice
• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice
• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment
• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment
• following tamoxifen treatment

hematopoietic system
• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice
• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice
• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment
• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment
• following tamoxifen treatment

cellular
• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice

endocrine/exocrine glands
• following tamoxifen treatment, mature medullary thymic epithelial cells undergo increased apoptosis compared to in wild-type mice
• following tamoxifen treatment, medullary thymic epithelial cells are reduced compared to in wild-type mice
• mature medullary thymic epithelial cells are more affected than presumptive medullary thymic epithelial cell precursors following tamoxifen treatment
• however, cortical thymic epithelial cells are not significantly reduced following tamoxifen treatment
• following tamoxifen treatment


Mouse Genome Informatics
cn18
    Lhx2tm1Monu/Lhx2tm1Dra
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair
• unable to develop beyond Sub-stage III and assemble a normal hair shaft


Mouse Genome Informatics
cn19
    Lhx2tm1Monu/Lhx2tm1Monu
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair
• unable to develop beyond Sub-stage III and assemble a normal hair shaft


Mouse Genome Informatics
cn20
    Supv3l1tm2.1Jkl/Supv3l1tm2.2Jkl
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Thymic atrophy in Supv3l1tm2.1Jkl/Supv3l1tm2.2Jkl Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging
• mice die by 15 weeks of age
• tamoxifen-treated mice die by 6 weeks of age

immune system
• in the lungs in tamoxifen-treated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• more than 10-fold in tamoxifen-treated mice
• chronic and acute in untreated and tamoxifen-treated mice

growth/size
• in tamoxifen-treated mice

adipose tissue
• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

respiratory system
• chronic and acute in untreated and tamoxifen-treated mice
• thickened in in tamoxifen-treated mice and untreated mice

muscle
• mice exhibit sarcopenia atrophy that develops more rapidly in tamoxifen treated mice

skeleton
• mice exhibit kyphosis that develops more rapidly in tamoxifen treated mice

endocrine/exocrine glands
• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

cardiovascular system
• tamoxifen-treated mice exhibit focal vascular ectasia in the skin unlike in untreated mice
• mice treated topically with tamoxifen exhibit dilated vasculature at the site of application

behavior/neurological
• locomotor functions fail in moribund mice

digestive/alimentary system
• tamoxifen-treated mice exhibit an increase in apoptosis compared to untreated mice

hematopoietic system
• in the lungs in tamoxifen-treated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• more than 10-fold in tamoxifen-treated mice

cellular
• in the lungs in tamoxifen-treated mice

integument
N
• unlike in Supv3l1tm2Jkl/Supv3l1tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal hair growth (J:144991)
• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice
• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice
• tamoxifen treated mice exhibit focal vascular ectasia, reduced adipose tissue, and atrophic muscle layer in the skin unlike in untreated mice
• apoptosis rates in the basal layer are increased in tamoxifen-treated mice compared to in untreated mice
• mild in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen
• at the site of tamoxifen application when applied directly to the skin
• hypergranulosis develops in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen
• in tamoxifen-treated mice
• in tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin
• at the site of tamoxifen application when applied directly to the skin
• on the skin and tails of tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin


Mouse Genome Informatics
cn21
    St14tm2Bug/St14tm3Bug
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are moribund within 9 to 10 days of tamoxifen treatment unlike similarly treated control mice

digestive/alimentary system
• tamoxifen-treated mice exhibit disruption of tight junctions unlike similarly treated wild-type mice
• tamoxifen-treated mice exhibit dissolution of tissue architecture and pronounced edema of crypts and submucosa in the large intestine unlike in similarly treated control mice
• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit a loss of intestinal barrier and increased intestinal permeability unlike similarly treated control mice
• tamoxifen-treated mice exhibit a 1.5-fold increase in epithelial cell transit through colonic crypts compared with similarly treated control mice
• tamoxifen-treated mice exhibit an increase in intestinal cell turnover compared with similarly treated control mice
• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

craniofacial
• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice

endocrine/exocrine glands
• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice

growth/size
• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice
• in tamoxifen-treated mice despite normal food ingestion
• in tamoxifen-treated mice

homeostasis/metabolism
• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

integument
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit follicular hyperplasia compared with similarly treated control mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit retention and hyperproliferative ichthyosis unlike similarly treated control mice
• tamoxifen-treated mice exhibit dermal fibrosis unlike similarly treated control mice


Mouse Genome Informatics
cn22
    Supv3l1tm2Jkl/Supv3l1tm2Jkl
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Kyphosis and scaling on feet develop in Supv3l1tm2Jkl/Supv3l1tm2Jkl Tg(CAG-cre/Esr1*)5Amc/0 mice following tamoxifen treatment

mortality/aging
• mice die by 15 weeks of age
• tamoxifen-treated mice die by 6 weeks of age

immune system
• in the lungs in tamoxifen-treated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• more than 10-fold in tamoxifen-treated mice
• chronic and acute in untreated and tamoxifen-treated mice

growth/size
• in tamoxifen-treated mice

adipose tissue
• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice

respiratory system
• chronic and acute in untreated and tamoxifen-treated mice
• thickened in in tamoxifen-treated mice and untreated mice

muscle
• mice exhibit sarcopenia atrophy that develops more rapidly in tamoxifen treated mice

skeleton
• mice exhibit kyphosis that develops more rapidly in tamoxifen treated mice

endocrine/exocrine glands
• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele

cardiovascular system
• tamoxifen-treated mice exhibit focal vascular ectasia in the skin unlike in untreated mice
• mice treated topically with tamoxifen exhibit dilated vasculature at the site of application

behavior/neurological
• locomotor functions fail in moribund mice

digestive/alimentary system
• tamoxifen-treated mice exhibit an increase in apoptosis compared to untreated mice

hematopoietic system
• in the lungs in tamoxifen-treated mice
• mice exhibit thymic atrophy that develops more rapidly in tamoxifen treated mice
• 6-fold in tamoxifen-treated mice compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit decreased DN2, DN3, and DN4 cells compared to mice heterozygous for the floxed allele
• in tamoxifen-treated mice
• more than 10-fold in tamoxifen-treated mice

cellular
• in the lungs in tamoxifen-treated mice

integument
N
• unlike in Supv3l1tm2Jkl/Supv3l1tm2Jkl floxed Tg(Mx1-cre)1Cgn mice, tamoxifen-treated mice exhibit normal hair growth (J:144991)
• mice exhibit adipose tissue loss that develops more rapidly in tamoxifen treated mice
• in tamoxifen-treated mice, the numbers of sebaceous glands is reduced compared to in untreated mice
• tamoxifen treated mice exhibit focal vascular ectasia, reduced adipose tissue, and atrophic muscle layer in the skin unlike in untreated mice
• apoptosis rates in the basal layer are increased in tamoxifen-treated mice compared to in untreated mice
• mild in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen
• at the site of tamoxifen application when applied directly to the skin
• hypergranulosis develops in tamoxifen-treated mice and at the site of application in mice treated topically with tamoxifen
• in tamoxifen-treated mice
• in tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin
• at the site of tamoxifen application when applied directly to the skin
• on the skin and tails of tamoxifen-treated mice and at the site of tamoxifen application when applied directly to the skin


Mouse Genome Informatics
cn23
    Mcattm1.1Ssmi/Mcattm1.1Ssmi
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Hair loss and dry skin in tamoxifen treated Mcattm1.1Ssmi/Mcattm1.1Ssmi Tg(CAG-cre/Esr1*)5Amc/0 mice

mortality/aging
• severely affected tamoxifen-treated mice develop pruritus that leads to self-inflicted scratch wounds and necessitates euthanasia
• tamoxifen-treated mice that do not require euthanasia exhibit mean survival time of 293 days post-induction

hematopoietic system
• in some tamoxifen-treated mice
• in some tamoxifen-treated mice
• in some tamoxifen-treated mice
• in some tamoxifen-treated mice
• in some tamoxifen-treated mice
• in some tamoxifen-treated mice
• tamoxifen-treated mice that develop anemia exhibit increased number and size of reticulocyte compared with control mice
• in some tamoxifen-treated mice
• minor in some female tamoxifen-treated mice (J:192213)
• minor in some female tamoxifen-treated mice (J:192213)
• myeloid hematopoiesis in the bone marrow of some tamoxifen-treated mice
• in some tamoxifen-treated mice
• in tamoxifen-treated mice
• anemic tamoxifen-treated mice exhibit reduced red blood cell lifespan compared with control mice

behavior/neurological
N
• tamoxifen-treated mice exhibit normal balance and motor coordination (J:192213)
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• severely affected tamoxifen-treated mice develop pruritus that leads to self-inflicted scratch wounds and necessitates euthanasia
• shivering in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• reduced exploration and overall activity in an open field test in tamoxifen-treated mice
• tamoxifen-treated mice walk with splayed hind limbs and drag their posterior unlike control mice
• tamoxifen-treated mice on a constantly spinning rotarod exhibit reduced endurance compared with control mice

homeostasis/metabolism
• tamoxifen-treated mice on a constantly spinning rotarod exhibit reduced endurance compared with control mice
• tamoxifen-treated mice exhibit elevated plasma lactate and ketone bodies compared with control mice
• in tamoxifen-treated mice
• decreased in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• tamoxifen-treated mice exhibit compromised fatty acid synthesis due to reduced availability of precursors for lipoylation of key mitochondrial enzymes compared with control mice
• in tamoxifen-treated mice

integument
• in tamoxifen-treated mice
• beginning 3 to 4 months after tamoxifen-treatment, coats have lost their normal luster compared with controls
• beginning 3 to 4 months after tamoxifen-treatment eventually resulting in severe baldness
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in severely affected tamoxifen-treated mice that leads to self-inflicted scratch wounds, necessitating euthanasia

digestive/alimentary system
N
• tamoxifen-treated mice exhibit normal digestion (J:192213)
• from prolapsed rectum in anemic tamoxifen-treated mice
• however, no blood is observed in the feces
• in 9 of 10 anemic tamoxifen-treated mice

cardiovascular system
• from prolapsed rectum in anemic tamoxifen-treated mice
• however, no blood is observed in the feces

growth/size
• tamoxifen-treated mice fail to gain weight
• after 6 months in tamoxifen-treated mice

immune system
• minor in some female tamoxifen-treated mice (J:192213)
• minor in some female tamoxifen-treated mice (J:192213)
• myeloid hematopoiesis in the bone marrow of some tamoxifen-treated mice
• lymphoid atrophy in some tamoxifen-treated mice
• in tamoxifen-treated mice

adipose tissue
• in tamoxifen-treated mice
• in tamoxifen-treated mice

cellular
• tamoxifen-treated mice exhibit compromised mitochondrial respiration due to defects in protein lipoylation and respiratory complexes compared with wild-type mice
• tamoxifen-treated mice exhibit compromised mitochondrial respiration due to defects in protein lipoylation and respiratory complexes compared with wild-type mice

muscle
• increased glycogen and lactate levels in skeletal muscle of tamoxifen-treated mice
• in tamoxifen-treated mice

skeleton
• in tamoxifen-treated mice


Mouse Genome Informatics
cn24
    Mecp2tm2Bird/Mecp2+
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 4 to 12 months of age, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition) (J:118365)
• however, tamoxifen treatment after the onset of symptoms reverses symptom progression (J:118365)
• at 4 to 12 months of age (J:118365)
• however, tamoxifen treatment after the onset of symptoms reverses symptom progression (J:118365)
• at 4 to 12 months of age (J:118365)
• however, tamoxifen treatment after the onset of symptoms reverses symptom progression (J:118365)

nervous system
• mice develop a reduction in long term potentiation (J:118365)
• however, treatment with tamoxifen returns long term potentiation to normal levels (J:118365)

respiratory system
• at 4 to 12 months of age (J:118365)
• however, tamoxifen treatment after the onset of symptoms reverses symptom progression (J:118365)

growth/size
• mice exhibit excess weight gain (J:118365)
• however, tamoxifen treatment after the onset of symptoms reverses weight gain (J:118365)


Mouse Genome Informatics
cn25
    Mecp2tm2Bird/Y
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 9 of 17 mice treated with tamoxifen at 3 to 4 weeks of age die soon after treatment (J:118365)
• however, tamoxifen-tocixity is not responsible for observed deaths, 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age have a normal life span, and mice treated with tamoxifen from week 12 to 17 exhibit normal lethality (J:118365)

behavior/neurological
N
• the surviving 8 of 17 mice treated with tamoxifen at 3 to 4 weeks of age exhibit normal behavior/neurological phenotypes (J:118365)
• at 12 weeks mice display low stance, inertia, tremor, arrhythmic breathing, splayed himdlimb and moderate hindlimb clasping (J:118365)
• during the last 4 weeks of life, mice exhibit a progressive development of RTT-like symptoms (inertia, gait, hindlimb clasping, tremor, irregular breathing and poor general condition) (J:118365)
• mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms (J:118365)
• at 12 weeks, mice display moderate hindlimb clasping (J:118365)
• mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms (J:118365)
• at 12 weeks (J:118365)
• mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms (J:118365)

respiratory system
• at 12 weeks (J:118365)
• mice treated with tamoxifen at 12 to 17 weeks of age exhibit only mild RTT-like symptoms (J:118365)


Mouse Genome Informatics
cn26
    Recktm1Ito/Recktm1.1Noda
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice treated with tamoxifen at E11 die after E15.5

cardiovascular system
• at E15.5, blood vessels in tamoxifen-treated mice are large and irregularly shaped compared to in wild-type mice
• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice
• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice
• at E15.5, blood vessels in tamoxifen-treated mice are large and irregularly shaped compared to in wild-type mice
• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice
• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice
• in tamoxifen-treated mice
• at E15.5 in tamoxifen-treated mice

growth/size
• at E15.5 in tamoxifen-treated mice

liver/biliary system
• the blood vessels in the livers of tamoxifen-treated mice exhibit larger luminal spaces than in wild-type mice

nervous system
• brain vasculature in tamoxifen-treated mice is disorganized and interrupted by large spaces and cavities unlike in wild-type mice

integument
• at E15.5 in tamoxifen-treated mice


Mouse Genome Informatics
cn27
    Nrg1tm3Cbm/Nrg1tm3Cbm
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• small diameter with degeneration of the outer capsule in tamoxifen-treated mice
• however, innervation is normal
• in tamoxifen-treated mice

behavior/neurological
• tamoxifen-treated mice hang on to an inverted grid 3 to 4 times less than controls mice
• strongly impaired in a beam-walking test

nervous system
• small diameter with degeneration of the outer capsule in tamoxifen-treated mice
• however, innervation is normal
• in tamoxifen-treated mice


Mouse Genome Informatics
cn28
    Rettm2(RET)Heno/Rettm1Cos
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E15.5 a nearly complete elimination of the enteric ganglia in the colon when treated with 4-OHT


Mouse Genome Informatics
cn29
    Rettm2(RET)Heno/Rettm2(RET)Jmi
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• oligoganglionic gut, puncta of nerve fiber and cell body staining are frequently observed in the interganglionic spaces with incomplete penetrance

embryogenesis

nervous system


Mouse Genome Informatics
cn30
    Plxnd1tm1.1Tmj/Plxnd1tm1.1Tmj
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• tamoxifen-treated retinas exhibit reduced angiogenesis and hemorrhages compared to in wild-type mice
• tamoxifen-treated retinas exhibit reduced angiogenesis compared to in wild-type mice
• vascular invasion of tamoxifen-treated endothelial cells into matrigel plugs treated with endothelial cell growth factor is deficient compared to that of wild-type cells
• tamoxifen-treated retinas exhibit hemorrhages unlike wild-type retinas

vision/eye
• tamoxifen-treated retinas exhibit reduced angiogenesis and hemorrhages compared to in wild-type mice

cellular
• vascular invasion of tamoxifen-treated endothelial cells into matrigel plugs treated with endothelial cell growth factor is deficient compared to that of wild-type cells


Mouse Genome Informatics
cn31
    Pou4f2tm4Whk/Pou4f2+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• reduced cross-sectional area by 48.8% in 3 months after a 5 day course of tamoxifen treatment
• cross-sectional area reduced to 19.7% of controls at ten months after a 5 day course of tamoxifen treatment
• axons disorganized
• progressive degeneration over the course of ten months after a 5 day course of tamoxifen treatment
• severe axon degeneration and vacuolation
• empty or abnormal myelin sheaths
• 60% reduction in the number of cells of the ganglion layer one month after a 5 day course of tamoxifen treatment
• 33% of time spent in the light as opposed to 6% for controls after 1-2 hours of dark adaptation

nervous system
• reactive gliosis triggered one month after a 5 day course of tamoxifen treatment
• reduced cross-sectional area by 48.8% in 3 months after a 5 day course of tamoxifen treatment
• cross-sectional area reduced to 19.7% of controls at ten months after a 5 day course of tamoxifen treatment
• axons disorganized
• progressive degeneration over the course of ten months after a 5 day course of tamoxifen treatment
• severe axon degeneration and vacuolation
• empty or abnormal myelin sheaths


Mouse Genome Informatics
cn32
    Fktntm1Kcam/Fktntm1Kcam
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• iliopsoas muscle from mice treated with tamoxifen show indications of dystrophic disease
• variations in fiber size
• necrosis
• increase in centrally nucleated fibers

homeostasis/metabolism
• levels begin to rise at 14 weeks of age and are significantly elevated at 16-20 weeks after tamoxifen treatment at 10 weeks of age

growth/size
N
• normal body weight at 4- 20 weeks of age after tamoxifen treatment (J:187144)

behavior/neurological
N
• normal forelimb grip strength at 4-20 weeks of age after tampxifen treatment (J:187144)
• normal open field activity at 4-20 weeks of age after tampxifen treatment (J:187144)


Mouse Genome Informatics
cn33
    Ppp2r1atm1.1Wltr/Ppp2r1atm1.2Wltr
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6 * CBA * FVB/NCrl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die 6 days after tamoxifen treatment

behavior/neurological
• tamoxifen-treated mice exhibit difficulty walking compared with control mice
• in tamoxifen-treated mice

growth/size
• in tamoxifen-treated mice beyond the initial drop associated with tamoxifen treatment alone


Mouse Genome Informatics
cn34
    Bub1tm1Ssta/Bub1tm1.1Ssta
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• sister chromatid cohesion is defective in tamoxifen-treated mouse embryonic fibroblasts
• the spindle assembly checkpoint is defective in tamoxifen-treated mouse embryonic fibroblasts
• unlike untreated cells, tamoxifen-treated mouse embryonic fibroblasts stop proliferating in culture


Mouse Genome Informatics
cn35
    Bub1tm1Ssta/Bub1tm1Ssta
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• after mice are treated with tamoxifen for 8 weeks, tubules exhibit decreased celullarity and diameter (J:128455)
• tubules containing only Sertoli cells are often observed (J:128455)
• after mice are treated with tamoxifen for 8 weeks, testis weight is decreased by 50% of wild-type (J:128455)
• after mice are treated with tamoxifen for 8 weeks, mitotic clusters of cells observed are often stuck in anaphase and abnormal chromosome content is observed (J:128455)
• after mice are treated with tamoxifen for 8 weeks, no male germ cells are observed (J:128455)
• after mice are treated with tamoxifen for 8 weeks, sperm production is reduced by 80% of wild-type (J:128455)
• after treated with tamoxifen for 4 weeks, adult males become infertile (J:128455)

cellular
• after mice are treated with tamoxifen for 8 weeks, male testes have reduced mitotic index

growth/size
• when mice are treated with tamoxifen beginning at E10.5, by E18.5 mice resemble E10.5 to E11.5 mice
• when mice are treated with tamoxifen beginning at E10.5, by E18.5 mice resemble E10.5 to E11.5 mice

endocrine/exocrine glands
• after mice are treated with tamoxifen for 8 weeks, tubules exhibit decreased celullarity and diameter (J:128455)
• tubules containing only Sertoli cells are often observed (J:128455)
• after mice are treated with tamoxifen for 8 weeks, testis weight is decreased by 50% of wild-type (J:128455)


Mouse Genome Informatics
cn36
    Inpp5etm1.1Ssch/Inpp5etm1.2Ssch
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• mice display increased body weight after tamoxifen treatment

renal/urinary system
• glomerular cysts are seen in 6 month old tamoxifen treated mice

vision/eye
• after tamoxifen treatment the retinal photoreceptor layer is completely absent


Mouse Genome Informatics
cn37
    Edn2tm1.1Nat/Edn2tm1.1Nat
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in mice treated with tamoxifen at P0
• in mice treated with tamoxifen at P0
• however, adult mice treated with tamoxifen exhibit normal survival

homeostasis/metabolism
• blood pH is more acidic in tamoxifen-treated mice
• in tamoxifen-treated mice
• in mice treated with tamoxifen at P0 or 6 weeks of age
• in mice treated with tamoxifen at P0 or 6 weeks of age
• decreased body temperature in response to cold exposure in mice treated with tamoxifen
• in tamoxifen-treated mice
• blood pH is more acidic in tamoxifen-treated mice

growth/size
• after 10 weeks of tamoxifen-induced activation
• in mice treated with tamoxifen at P0 or 6 weeks of age
• in mice treated with tamoxifen at P0 or 6 weeks of age

respiratory system
• tamoxifen-treated mice exhibit enlarged air spaces with simplification of the alveolar structure
• simplified structure in tamoxifen-treated mice

adipose tissue
• after 10 weeks of tamoxifen-induced activation


Mouse Genome Informatics
cn38
    Dscamtm1Pfu/Dscamtm1Pfu
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped
• following tamoxifen treatment at P0
• following tamoxifen treatment at P0 2?3 fasciculated groups of melanopsin positive retinal ganglion cells are seen in each retina

nervous system
• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped
• following tamoxifen treatment at P0, 2?3 fasciculated groups of retinal ganglion cells are seen in each retina
• however with tamoxifen treatment at P0 or in adults no fasiculation of amacrine cell neurites is seen
• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped
• following tamoxifen treatment at P0
• following tamoxifen treatment at P0 2?3 fasciculated groups of melanopsin positive retinal ganglion cells are seen in each retina

cellular
• following tamoxifen treatment at E13 or E16 dopaminergic amacrine cells and neurites are clumped
• following tamoxifen treatment at P0, 2?3 fasciculated groups of retinal ganglion cells are seen in each retina
• however with tamoxifen treatment at P0 or in adults no fasiculation of amacrine cell neurites is seen


Mouse Genome Informatics
cn39
    Sdhdtm1Jlob/Sdhdtm2Jlob
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• in tamoxifen-treated mice

nervous system
N
• tamoxifen-treatment does not affect brain catecholaminergic neurons matured at birth (J:186713)
• tamoxifen-treated mice exhibit a trend towards degeneration of the carotid body

cardiovascular system
• tamoxifen-treated mice exhibit a trend towards degeneration of the carotid body

tumorigenesis
N
• tamoxifen-treated mice do not develop tumors (J:186713)


Mouse Genome Informatics
cn40
    Kcnq1ot1tm2.1Ckan/Kcnq1ot1+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SD7
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• loss of methylation in the somatic differentially methylated regions following tamoxifen treatment at E8.5 when the Kcnq1ot1 allele is inherited paternally
• loss of imprinting of ubiquitously imprinted genes following tamoxifen treatment at E8.5 when the Kcnq1ot1 allele is inherited paternally
• however, silencing of placental-specific imprinted genes is variably maintained
• no alteration of imprinting status when the Kcnq1ot1 allele is inherited maternally


Mouse Genome Informatics
cn41
    Numa1tm1.1Dwc/Numa1tm1.1Dwc
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Spindle defects in primay Numa1tm1.1Dwc/Numa1tm1.1Dwc Tg(CAG-cre/Esr1*)5Amc/0 fibroblasts

cellular
N
• despite spindle defects, bulk chromosome segregation is largely normal (J:146214)
• tamoxifen-treated mouse embryonic fibroblasts (MEFs) exhibit detachment of microtubule-nucleating structures from the ends of the mitotic spindles unlike wild-type cells
• 50% of metaphase-like tamoxifen-treated MEFs have at least one centrosome that is not clearly associated with a spindle pole unlike in wild-type cells
• tension between sister kinetochores in pole-focused spindles in tamoxifen-treated MEFs exposed to MG132 is 33% less than in wild-type cells
• more like tamoxifen-treated MEFs exhibit pole defocusing and centrosome detachment than in wild-type cells
• tamoxifen-treated mouse embryonic fibroblasts (MEFs) fail to increase in number after release from growth arrest unlike wild-type cells


Mouse Genome Informatics
cn42
    Six3tm2Gco/Six3tm2.1Gco
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• defects are observed starting at E10.5
• reduction in size of invaginating lens pit is observed in mildly and moderately affected embryos
• at E14.5, some embryos have an abnormally persistent lens stalk
• differentiation of lens is not affected in mildly or moderately affected mutant lenses
• in severely affected lenses at E10.5, no lens-like structures are present
• at E12.5, in mild cases, lens vesicle is small but relatively normal, small and abnormal in moderated cases and completely absent in severely affected embryos and neuroretinal is malformed also
• at E14.5 some embryos show disorganized lens fibers
• lens is absent in some mutants
• cataracts are present in some mice
• some mice show drastically reduced lens size
• shape of vesicle is defective


Mouse Genome Informatics
cn43
    Gdnftm1Bbd/Gdnftm1Jlob
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tyrosine hydroxylase positive neurons are diminished by more than half 210 days after tamoxifen-treatment
• tamoxifen treatment leads to the death of catecholaminergic neurons in the brain
• 210 days after tamoxifen treatment, there is a substantial lose (about 50%) of tyrosine hydroxylase positive neurons in the substantia nigra adult mice
• there is also a drop in the total number of neurons in the substantia nigra after tamoxifen treatment
• 210 days after tamoxifen treatment, there is a substantial lose (about 2.5-fold) of tyrosine hydroxylase positive neurons in the ventral tegmentum of adult mice
• there is also a drop in the total number of neurons in the ventral tegmentum after tamoxifen treatment
• neurons are diminished in the locus ceruleus 210 days after tamoxifen treatment
• fiber density of tyrosine hydroxylase positive neurons are diminished 210 days after tamoxifen treatment
• fiber density of tyrosine hydroxylase positive neurons are diminished 210 days after tamoxifen treatment

behavior/neurological
• 100 days after tamoxifen injection, mice have reduced activity in open field tests with about 25% less activity
• resting time of mice in open field tests increases significantly 100 days after tamoxifen treatment
• this hypoactivity worsens with the passage of time

cardiovascular system
• tyrosine hydroxylase positive neurons are diminished by more than half 210 days after tamoxifen-treatment


Mouse Genome Informatics
cn44
    Ate1tm1Avar/Ate1tm2.1Avar
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 15% (18 of 119 mice) die over 42 days after TM treatment
• 46% of mice younger than 30 days at the beginning of TM treatment die within 42 days after TM treatment
• 12% of mice die if they are older than 30 days (up to 56 days) at the beginning of TM treatment

growth/size
• decreased growth
• attaining only 70% of normal weight
• no decrease in their consumption of food
• during the first 3 weeks after TM treatment, rapid loss of weight
• all the phenotypes below are induced by tamoxifen (TM) treatment
• 5% smaller average body length (p<0.08)
• resistant to high-fat diet induced obesity

behavior/neurological
• higher than normal food intake
• within a week after TM treatment increased food consumption (125%) which continues up to 8 months
• 53% (95 of 180) of surviving mice appear ''scruffy'', versus 3% (8 of 244) of wild type
• enhanced startle response
• most mice (96 of 180) are strikingly hyperkinetic in the open field test
• travel 3-fold greater distance
• 10-fold higher propensity for seizures
• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice

adipose tissue
• contain little or no visceral fat
• strikingly lower content of the peritoneal white adipose tissue (WAT), on average only 16% of WAT in wild type mice
• decrease average diameter of intrascapular brown adipocytes
• the average diameter of WAT adipocytes is 30% of that of the wild type mice
• exhibit ectopic induction of the uncoupling protein 1 (Ucp1) in white adipose tissue

homeostasis/metabolism
• resistant to high-fat diet induced obesity
• strongly hypersensitive to cold
• decreased fasting blood glucose level (88.6 mg/dl versus 125.3 mg/dl)
• lower glucose levels 6 hr after administration of glucose (80.9 mg/dl versus 109.7 mg/dl)
• no other significant differences in blood composition
• lower core body temperature on average 35.1C (36.7C in wild type)
• the average water content and dry weight was 80.5% and 19.5%, respectively, versus 79.9% and 20.1% of wild type brains
• increased metabolic rate (resting metabolic rate, RMR)
• consume on average 46.12 ml of oxygen per kg per min, versus 29.3 ml of oxygen per kg per min
• decreased expression of mRNA encoding proopiomelanocortin (POMC) in hypothalami
• normal respiratory exchange ratio (RER)

nervous system
• 10-fold higher propensity for seizures
• 3.1% mice (38 of 1,232) have tonic-clonic seizures during routine cage changes and handling of mice, versus 0.3% of wild type mice
• brains appear swollen and bigger
• the average brain weight, as a percentage of total body weight (TBW) are 3.09%, versus 1.96% of wild type mice
• no differences in cell proliferation (5-ethynyl-29-deoxyuridine (EdU) incorporation)

skeleton
• the skulls appear to be thinner and softer
• 66% (109 of 180) of surviving mice have a kyphotic posture, versus 2% (5 of 244) of wild type

reproductive system
• testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis (J:155421)
• lumens of seminiferous tubules contain few sperm cells, in a disorganized arrangement (J:155421)
• lumens of seminiferous tubules contain few sperm cells (J:155421)
• males are infertile (J:155421)

cardiovascular system
• hearts are disproportionately large

renal/urinary system
• kidneys are disproportionately large

cellular
• increased retention of 14C in their brains, livers, spleens, kidneys and hearts

digestive/alimentary system
• increased intestinal import of 14C-protein

pigmentation
• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair

endocrine/exocrine glands
• testis extracts contain the 85-kDa fragment of poly(ADP-ribose)-polymerase (PARP) but no full-length PARP, indicating extensive apoptosis (J:155421)

craniofacial
• the skulls appear to be thinner and softer

integument
• 10% (8 of 80) of surviving mice develop patches of red hair among their normally black hair


Mouse Genome Informatics
cn45
    Rapgef2tm1.1Hous/Rapgef2tm1.1Hous
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most mice treated with tamoxifen at E11.5 and E13.5 die E17.5 and E18.5 with remaining mice dying at E19.5 to E10.5
• however, mice treated with tamoxifen at E17.5 and E19.5 exhibit the same lethality as in similarly treated Rapgef2tm1.1Hous homozygotes

hematopoietic system
• mice treated with tamoxifen at E11.5 and E13.5 exhibit impaired fetal liver hematopoiesis with reduced differentiation of erythroid progenitor cells compared with similarly treated Rapgef2tm1.1Hous homozygotes
• at E16.5 in the livers of mice treated with tamoxifen at E11.5 and E13.5

cardiovascular system
• at E17.5, mice treated with tamoxifen at E11.5 and E13.5 lack major embryonic blood vessels unlike wild-type mice

growth/size
• in mice treated with tamoxifen at E17.5 and E19.5

liver/biliary system
• at E16.5 in mice treated with tamoxifen at E11.5 and E13.5

integument
• at E17.5 in mice treated with tamoxifen at E11.5 and E13.5


Mouse Genome Informatics
cn46
    Wnt5atm1.1Tpy/Wnt5atm1.1Tpy
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• abnormal wound channels containing fewer invaginations at day 6 and lacking crypt like structures at day 8 are seen after colonic mucosal injury in tamoxifen treated mice

homeostasis/metabolism
• abnormal wound channels containing fewer invaginations at day 6 and lacking crypt like structures at day 8 are seen after colonic mucosal injury in tamoxifen treated mice


Mouse Genome Informatics
cn47
    Setd8tm1.1Dare/Setd8tm1.2Dare
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S1/Sv * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• tamoxifen-treated embryonic stem cells exhibit global chromosomal decondensation at interphase compared to in wild-type cells
• tamoxifen-treated embryonic stem cells exhibit increased DNA damage compared to wild-type cells
• tamoxifen-treated embryonic stem cells exhibit decreased DNA synthesis compared to in wild-type cells
• tamoxifen-treated embryonic stem cells exhibit a defect in cell growth at G2/M phase unlike wild-type cells
• 24 hours after tamoxifen treatment, embryonic stem cells undergo apoptosis unlike wild-type cells

homeostasis/metabolism
• tamoxifen-treated embryonic stem cells exhibit increased DNA damage compared to wild-type cells
• tamoxifen-treated embryonic stem cells exhibit decreased DNA synthesis compared to in wild-type cells


Mouse Genome Informatics
cn48
    Cxadrtm1.1Ics/Cxadrtm1.1Ics
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S2/SvPas * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice treated with tamoxifen at 4 weeks of age show a reduced tendency to freeze when transferred to a novel environment

cardiovascular system
• most discs are severely changed with disconnection between myofilaments and the presence of big vacuoles-containing parts of membranes in tamoxifen treated mice
• the outline of the junction is also changed with the distance between zonula adherens being wider and containing clot like contents in some areas
• complete atrioventricular block with temporal dissociation between atrial depolarization and ventricular depolarization in mice treated with tamoxifen at 4 weeks of age at 24 weeks after the last tamoxifen treatment

digestive/alimentary system
• atrophy and metaplastic phenotype are present as early as 3 weeks after tamoxifen treatment and is maintained up to 18 months after tamoxifen treatment
• duct-like tubular complexes replace the acinar cells in mice treated with tamoxifen at 4 weeks of age
• almost a complete lack of acinar cells in mice treated with tamoxifen at 4 weeks of age
• in mice treated with tamoxifen at 4 weeks of age
• dilated intestine in mice treated with tamoxifen at 4 weeks of age at up to 18 months after the last tamoxifen treatment

endocrine/exocrine glands
• in mice treated with tamoxifen at 4 weeks of age the pancreas consists of mainly adipose tissue in which apparently normal islets of Langerhans are interspersed
• atrophy and metaplastic phenotype are present as early as 3 weeks after tamoxifen treatment and is maintained up to 18 months after tamoxifen treatment
• duct-like tubular complexes replace the acinar cells in mice treated with tamoxifen at 4 weeks of age
• almost a complete lack of acinar cells in mice treated with tamoxifen at 4 weeks of age
• in mice treated with tamoxifen at 4 weeks of age
• dramatically smaller in mice treated with tamoxifen at 4 weeks of age at up to 18 months after the last tamoxifen treatment
• in tamoxifen treated mice 2 -3 days after the last treatment
• in tamoxifen treated mice 2 -3 days after the last treatment

hematopoietic system
• in tamoxifen treated mice 2 -3 days after the last treatment
• in tamoxifen treated mice 2 -3 days after the last treatment

immune system
• in tamoxifen treated mice 2 -3 days after the last treatment
• in tamoxifen treated mice 2 -3 days after the last treatment

muscle
• most discs are severely changed with disconnection between myofilaments and the presence of big vacuoles-containing parts of membranes in tamoxifen treated mice
• the outline of the junction is also changed with the distance between zonula adherens being wider and containing clot like contents in some areas


Mouse Genome Informatics
cn49
    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
cn50
    Ccnd1tm1Wbg/Ccnd1tm5.1Pisc
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
normal phenotype
• tamoxifen-treated mice exhibit no obvious abnormalities


Mouse Genome Informatics
cn51
    Syngap1tm2Geno/Syngap1+
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
behavior/neurological
• mice exhibit behavioral abnormalities as in Syngap1tm1Rlh heterozygotes
• untreated mice and mice treated with tamoxifen in adulthood spend increased time in open arms of an elevated plus maze compared with control mice
• untreated mice and mice treated with tamoxifen in adulthood exhibit absence of spontaneous alteration in a T-maze compared with control mice
• untreated mice and mice treated with tamoxifen in adulthood exhibit increased activity in an open field compared with control mice


Mouse Genome Informatics
cn52
    Alkbh4tm1Geno/Alkbh4tm1Geno
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
• increased frequency of multinucleation in tamoxifen-treated mouse embryonic fibroblasts due to aborted cytokinesis
• tamoxifen-treated mouse embryonic fibroblasts exhibit defects in the organization of the cleavage furrow, increased frequency of multinucleation due to aborted cytokinesis and increased centrosomes likely a consequence of polyploidy compared with control cells
• however, complementation with the wild-type protein rescues cytokinesis defects
• in tamoxifen-treated mouse embryonic fibroblasts


Mouse Genome Informatics
cn53
    Ccnd1tm1Wbg/Ccnd1tm5.1Pisc
Tg(CAG-cre/Esr1*)5Amc/0
Tg(MMTV-Erbb2)NK1Mul/0

involves: 129S2/SvPas * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen-treatment halts cancer progression and lowers tumor burden with increased senescence of tumor cells compared to in control mice


Mouse Genome Informatics
cn54
    Esco2tm1.1Ge/Esco2tm1.1Ge
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S2/SvPas * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• tamoxifen-treated mouse embryonic fibroblasts exhibit highly abnormal nuclear morphology with micronuclei and multilobulated nuclei
• chromosomes from tamoxifen-treated mouse embryonic fibroblasts exhibit railroad track morphology
• tamoxifen-treated mouse embryonic fibroblasts exhibit lagging chromosomes with reduced pericentric heterochromatin cohesion
• tamoxifen-treated mouse embryonic fibroblasts exhibit a 2.5-fold increase in mitotic index in asynchronously grown cultures
• tamoxifen-treated mouse embryonic fibroblasts fail to proliferate


Mouse Genome Informatics
cn55
    Cdc73tm1Btt/Cdc73tm1Btt
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die 20 days after administration of tamoxifen
• when tamoxifen is administered from E8.5 to E14.5

cellular
• after treatment of adults with tamoxifen, mice exhibit an increase in apoptotic cells in the salivary glands, tongue, stomach, intestine, liver and kidneys compared to in wild-type mice
• mouse embryonic fibroblast cells treated with tamoxifen exhibit increased apoptosis compared to wild-type cells
• in mouse embryonic fibroblast cells treated with tamoxifen

digestive/alimentary system
• after treatment of adults with tamoxifen, some mice develop dilation of the gastrointestinal tract
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen

endocrine/exocrine glands
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen (J:135255)
• after treatment of adults with tamoxifen (J:135255)
• after treatment of adults with tamoxifen, mice exhibit reduced submandibular and seminal vesicle secretion and a decrease in the number of tubular glands compared to wild-type mice

liver/biliary system
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

renal/urinary system
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen, mice exhibit necrotic cells in the liver and kidney likely due to multiorgan failure

respiratory system
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen, breathing is labored

homeostasis/metabolism
• after treatment of adults with tamoxifen, some mice develop ascites

nervous system
• when tamoxifen is administered from E8.5 to E14.5, development of the central nervous system is significantly delayed compared to in wild-type mice

behavior/neurological
• after treatment of adults with tamoxifen, mice exhibit slow reactions
• after treatment of adults with tamoxifen

muscle
• after treatment of adults with tamoxifen, mice exhibit muscle loss

adipose tissue
• after treatment of adults with tamoxifen
• after treatment of adults with tamoxifen

embryogenesis
• when tamoxifen is administered from E8.5 to E14.5, E10.5 and E12.5 or E12.5 and E14.5, embryos are smaller than normal

reproductive system
• after treatment of adults with tamoxifen (J:135255)
• after treatment of adults with tamoxifen (J:135255)

hematopoietic system
• after treatment of adults with tamoxifen

immune system
• after treatment of adults with tamoxifen

growth/size
• when tamoxifen is administered from E8.5 to E14.5, E10.5 and E12.5 or E12.5 and E14.5, embryos are smaller than normal
• after treatment of adults with tamoxifen

cardiovascular system
• after treatment of adults with tamoxifen

integument
• after treatment of adults with tamoxifen


Mouse Genome Informatics
cn56
    Lhx2tm1.1Lcar/Lhx2tm1Dra
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair
• unable to develop beyond Sub-stage III and assemble a normal hair shaft


Mouse Genome Informatics
cn57
    Lhx2tm1.1Lcar/Lhx2tm1.1Lcar
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• most mice shaved and treated with Tamoxifen at 3 weeks of age do not regrow hair
• unable to develop beyond Sub-stage III and assemble a normal hair shaft


Mouse Genome Informatics
cn58
    Pomctm2Low/Pomctm2Low
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Obesity in Pomctm2Low/Pomctm2Low Tg(CAG-cre/Esr1*)5Amc/0 females and weight loss following tamoxifen treatment

growth/size
• in vehicle treated mice
• however, tamoxifen treatment restores body fat
• in vehicle treated mice
• in vehicle treated mice
• mice treated with tamoxifen at P60 or P180 exhibit rapid weight loss for 3 weeks followed by a plateau and resumption of weight gain
• in vehicle-treated mice
• in male mice treated with tamoxifen at P60 or P180
• however, mice exhibit normal weight when with tamoxifen at P25 exhibit normal weight or when male mice are subjected to caloric restriction and returned to ad libitum feeding with tamoxifen treatment at P60
• in vehicle-treated mice
• in male mice treated with tamoxifen at P60 or P180
• however, mice exhibit normal weight when with tamoxifen at P25 exhibit normal weight or when male mice are subjected to caloric restriction and returned to ad libitum feeding with tamoxifen treatment at P60

homeostasis/metabolism
• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180
• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180
• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180
• regardless of tamoxifen treatment
• in vehicle treated mice and to a lesser extent in mice treated with tamoxifen at P180

adipose tissue
• in vehicle treated mice
• however, tamoxifen treatment restores body fat
• in vehicle treated male mice (J:194013)
• however, tamoxifen treatment at P25, P60 or P180 restores fat pad weight (J:194013)
• in vehicle treated mice
• however, tamoxifen treatment at P25, P60 or P180 restores fat pad weight
• in vehicle treated mice
• however, tamoxifen treatment at P60 or P180 restores fat pad weight

behavior/neurological
• in the first 2 to 3 weeks following tamoxifen-treatment
• following a 24 hour fast in vehicle treated mice
• however, tamoxifen restores fast-induced hyperphagia
• in vehicle treated mice
• however, tamoxifen treatment at P25, P60 or P180 restores daily food intake
• in vehicle treated mice
• however, tamoxifen treatment restores activity

liver/biliary system
• in vehicle treated mice
• however, tamoxifen treatment restores liver weight
• however, tamoxifen treatment restores liver fat content
• in vehicle treated mice


Mouse Genome Informatics
cn59
    Nrltm1Jcco/Nrltm1Jcco
Rhotm1Jlem/Rhotm1Jlem
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Rod reprogramming prevents retinal degeneration in tamoxifen treated Rhotm1Jlem/Rhotm1Jlem Nrltm1Jcco/Nrltm1Jcco Tg(CAG-cre/Esr1*)5Amc/0 mice

vision/eye
N
• photoreceptor death observed in Rhotm1Jlem homozygotes is prevented in tamoxifen-treated mice with preservation of rod cell bodies and inner segments and intact photopic b-wave over a wide range of flash intensities (J:193697)


Mouse Genome Informatics
cn60
    Mmp14tm1Hbh/Mmp14tm1.1Khol
Mmp15tm1Kohl/Mmp15tm1Kohl
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice
• at E12.5 in tamoxifen-treated mice starting at E7.5
• however, placenta develops normally in mice treated with tamoxifen at E12.5

endocrine/exocrine glands
N
• tamoxifen-treated mice exhibit normal mammary gland involution (J:167396)

cardiovascular system
• mice treated with tamoxifen at E7.5 exhibit compact structure, sparse vessels, and multiple dead cells around the fetal blood vessels unlike in wild-type mice


Mouse Genome Informatics
cn61
    Pappatm1Lex/Pappatm1Lex
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S5/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• reduced neointima formation following carotid ligation in tamoxifen-treated mice
• however, media area is normal

homeostasis/metabolism
• reduced neointima formation following carotid ligation in tamoxifen-treated mice
• however, media area is normal


Mouse Genome Informatics
cn62
    Egln1tm1Kael/Egln1tm1Kael
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants exposed to tamoxifen at E17.5 and 3 weeks after birth to induce cre expression begin dying suddenly around 10 weeks of age

growth/size
• by 10 weeks of age, mutants that are exposed to tamoxifen at E17.5 and 3 weeks after birth, are smaller

cardiovascular system
• 8- to 10-week old mutants treated with tamoxifen at E17.5 and 3 weeks after birth exhibit venous congestion
• the space between myocardial fibers is increased in mutants treated with tamoxifen at E17.5 and 3 weeks after birth
• cardiomyocytes of mutants treated with tamoxifen at E17.5 and 3 weeks after birth are enlarged, with occasional large nuclei
• mutants treated with tamoxifen at E17.5 and 3 weeks after birth consistently exhibit dilated cardiomyopathy
• mutants treated with tamoxifen at E17.5 and 3 weeks after birth exhibit increased contraction band necrosis indicative of early cardiac ischemia
• retroperitoneal hemorrhage is observed by 10 weeks of age in mutants exposed to tamoxifen at E17.5 and 3 weeks after birth

hematopoietic system
• mutants treated with tamoxifen at E17.5 and 3 weeks after birth show profound increases in red blood cell production associated with increased serum erythropoietin levels

muscle
• cardiomyocytes of mutants treated with tamoxifen at E17.5 and 3 weeks after birth are enlarged, with occasional large nuclei
• mutants treated with tamoxifen at E17.5 and 3 weeks after birth consistently exhibit dilated cardiomyopathy

integument
• by 10 weeks of age, mutants that are exposed to tamoxifen at E17.5 and 3 weeks after birth are erythematous and begin dying suddenly

homeostasis/metabolism
• mutants treated with tamoxifen at E17.5 and 3 weeks after birth show profound increases in red blood cell production associated with increased serum erythropoietin levels


Mouse Genome Informatics
cn63
    Ptpn11tm1Toa/Ptpn11+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• following tamoxifen treatment cultured bone marrow megakaryocyte-erythrocyte progenitor cells produce significantly fewer erythrocyte colony-forming unit colonies and slightly more erythroid burst-forming unit colonies
• following tamoxifen treatment cultured granulocyte-monocyte progenitor cells and common myeloid progenitor cells give rise to more cytokine independent colonies

immune system
• following tamoxifen treatment cultured granulocyte-monocyte progenitor cells and common myeloid progenitor cells give rise to more cytokine independent colonies


Mouse Genome Informatics
cn64
    Ewsr1tm2(FLI1*)Sblee/Ewsr1+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• after tamoxifen injection, within 4 to 6 days mice become moribund and die

cellular
• 24 hours after tamoxifen application MEF cultures begin to die and caspase-3 activity increases
• after tamoxifen injection, increase in TUNEL+ cells in epithelia

renal/urinary system
• after tamoxifen injection, increase in TUNEL+ cells in epithelia


Mouse Genome Informatics
cn65
    Ewsr1tm1Sblee/Ewsr1+
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no effects on survival even after 6 months following tamoxifien injection
• no phenotype of MEFS with tamoxifen


Mouse Genome Informatics
cn66
    Kdm5atm1Kael/Kdm5atm1Kael
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• in mouse embryonic fibroblasts treated with tamoxifen


Mouse Genome Informatics
cn67
    Mecomtm2.1Aspe/Mecomtm2.1Aspe
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• tamoxifen-treated mice lack long-term repopulating cells (or high proliferative potential colony-forming cells; HPP-CFC) unlike wild-type mice
• granulocyte and macrophage progenitors (CFU-G and CFU-M, respectively) are increase 3- to 4-fold compared with wild-type mice
• tamoxifen-treated mice exhibit fewer multipotent progenitors (CFU-GEMM) and granulocyte-macrophage progenitor (CFU-GM) compared with wild-type mice


Mouse Genome Informatics
cn68
    Gaktm2Legr/Gaktm2Legr
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within six days of tamoxifen treatment


Mouse Genome Informatics
cn69
    Sav1tm1.1Rjo/Sav1tm1.1Rjo
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• by 14 months of age


Mouse Genome Informatics
cn70
    Hdac3tm1Swh/Hdac3tm1.1Swh
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• several markers of DNA damage are increased in MEFs after tamoxifen treatment
• impaired cell cycle progression prior to metaphase in tamoxifen treated MEFs
• in MEFs following tamoxifen treatment


Mouse Genome Informatics
cn71
    Mdm4tm3Glo/Mdm4tm3.1Glo
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• tamoxifen treated adult mice are viable, do not appear sick, and do not display increased sensitivity to ionizing radiation


Mouse Genome Informatics
cn72
    Myogtm3Whk/Myogtm3Whk
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of the animals die before postnatal day 10

growth/size
• surviving homozygotes are noticeably smaller than controls (homozygous floxed littermates not carrying the Cre transgene) with normal myogenin expression
• at 12 weeks postnatal, homozygous null animals weigh 30% less than controls; at 6 weeks of age, null mice weighed 17.5 g compared to 20 g for controls

muscle
• in one pair of homozygous littermates, diaphragms were notably thinner than those of controls but the animals breathed normally


Mouse Genome Informatics
cn73
    Dicer1tm1Snj/Dicer1tm1Snj
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• at E14 to E16, tamoxifen treated mice exhibit increased cellular senescence in developing limbs compared to in wild-type mice


Mouse Genome Informatics
cn74
    Tbx1tm1Bld/Tbx1tm3Bld
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice
• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5
• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice
• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5


Mouse Genome Informatics
cn75
    Lmx1btm1Rjo/Lmx1btm1Witz
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• sparsely distributed corneal keratocytes, disorganized collagen fibrils, and wavy lamellae by 4 weeks after tamoxifen treatment
• by 4 weeks after tamoxifen treatment
• thinner by 4 weeks after tamoxifen treatment
• corneas become cloudy by 4 weeks after tamoxifen treatment

renal/urinary system
• dilated tubules filled with eosinophilic material are seen after tamoxifen treatment
• a severe degenerative phenotype with dilated tubules filled with eosinophilic material develops after tamoxifen treatment
• develops after tamoxifen treatment

behavior/neurological
• develops several weeks after tamoxifen treatment

cardiovascular system
• by 4 weeks after tamoxifen treatment


Mouse Genome Informatics
cn76
    Bmpr1atm1Bhr/Bmpr1atm2.1Bhr
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• tamoxifen-treated mice exhibit normal sclerotome formation (J:169133)


Mouse Genome Informatics
cn77
    Trp53tm1Glo/Trp53tm4Glo
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice survive longer than Trp53tm1Glo/Trp53tm4Glo mice

tumorigenesis
• tamoxifen-treated lymphomas exhibit decreased apoptosis response compared with tumors from Trp53tm3.1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• tamoxifen-treated tumors exhibit decreased cell proliferation compared with control samples
• angiosarcomas treated with tamoxifen exhibit increased senescence compared with tamoxifen-treated angiosarcomas from Trp53tm3.1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• tamoxifen-treatment induces apoptosis and senescence in giant-cell sarcoma
• in tamoxifen-treated mice


Mouse Genome Informatics
cn78
    Trp53tm3.1Glo/Trp53tm4Glo
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice survive longer than Trp53tm3.1Glo/Trp53tm4Glo mice

tumorigenesis
• tamoxifen-treated lymphomas exhibit increased apoptosis response compared with tumors from Trp53tm1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• 3 of 5 tamoxifen-treated lymphomas exhibit senescence unlike in tumors from Trp53tm1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• tamoxifen-treated angiosarcomas and lymphomas exhibit senescence
• tamoxifen-treated mice exhibit little to no tumor growth unlike in control mice


Mouse Genome Informatics
cn79
    Omgtm1.2Bzh/Omgtm1.2Bzh
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
phenotype not analyzed
• mice were used for expression analysis


Mouse Genome Informatics
cn80
    Mstntm1Swel/Mstntm1Swel
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129S7/SvEvBrd-Hprt1 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• the mean cross-sectional area of an individual quadriceps fibers in tamoxifen treated mice is 42% greater than in treated controls
• after 3 months of tamoxifen treatment muscle mass is increased by 25% compared to untreated mice and treated wild-type mice in the gastrocnemius and quadriceps of males and females


Mouse Genome Informatics
cn81
    Gt(ROSA)26Sortm1(Smo/EYFP)Amc/?
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• following tamoxifen treatment, all mice are dead by 18 weeks of observation unlike untreated mice and Ptch1tm1Mps heterozygotes

tumorigenesis
• following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks
• found in 27% of mice and 40% of mice following tamoxifen treatment
• present without tamoxifen treatment (average number 3)
• following tamoxifen treatment, the multiplicity of tumors is increased (average number 7)
• mostly confined to rear thigh and abdominal wall
• following tamoxifen treatment, tumors are detected in skeletal muscle of the head, neck, tongue and paratesticular regions
• following tamoxifen treatment at P10, age of onset is accelerated to week 5 compared to week 9 in untreated mice

digestive/alimentary system
• diverticular harmatomatous lesions in the intestine occur at a higher rate following treatment with tamoxifen (20% without treatment and 80% following treatment)
• diverticular harmatomatous lesions in the stomach occur at a higher rate following treatment with tamoxifen (less than 5% of mice after treatment)

endocrine/exocrine glands
• cystic metaplastic lesions are observed with increased frequency following tamoxifen treatment

integument
• following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks


Mouse Genome Informatics
cn82
    Rettm1Heno/Rettm2(RET)Heno
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tamoxifen-treated mice exhibit fewer enteric neurons than in similarly controls (Rettm1Heno/Ret+ Tg(CAG-cre/Esr1*)5Amc mice)


Mouse Genome Informatics
cn83
    Rettm1Heno/Rettm3.1(Bcl2l1)Heno
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• tamoxifen-treated mice exhibit decreased stool frequency compared with control mice
• 2 to 5 tamoxifen-treated mice exhibit hard feces that accumulates in the distal colon unlike in control mice
• tamoxifen-treated mice exhibit wet stool weight and water stool content compared with control mice

growth/size
• in tamoxifen-treated mice

nervous system
• 40% of tamoxifen-treated mice exhibit reduced enteric neurons compared with similarly treated control mice (Rettm1Heno/Ret+ Tg(CAG-cre/Esr1*)5Amc mice)
• tamoxifen-treated mice exhibit fewer NOS-expressing neurons compared to in control mice
• however, 60% of tamoxifen-treated mice exhibit normal enteric nervous system development


Mouse Genome Informatics
cn84
    Baxtm1Sjk/Baxtm1Sjk
Rettm1Heno/Rettm3.1(Bcl2l1)Heno
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tamoxifen-treated mice exhibit loss of enteric neurons unlike similarly treated control mice (Rettm1Heno/Ret+ Tg(CAG-cre/Esr1*)5Amc mice)


Mouse Genome Informatics
cn85
    Wnt9btm1.1Amc/Wnt9btm1.2Amc
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice treated with tamoxifen from E15.5 die by P90

renal/urinary system
• in mice treated with tamoxifen from E15.5 to P10
• however, mice treated with tamoxifen after P10 do not develop cysts


Mouse Genome Informatics
cn86
    Cxcl12tm1.1Ystz/Cxcl12tm1.2Ystz
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129X1/SvJ * C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• tamoxifen-treated mice exhibit an increase in the percentage of circulating neutrophils compared with wild-type mice
• in the bone marrow of tamoxifen-treated mice
• tamoxifen-treated mice exhibit a reduction in long term hematopoietic stem cells compared with wild-type mice
• tamoxifen-treated mice exhibit an increase in LSK cells in the bone marrow and peripheral blood compared with wild-type mice
• tamoxifen-treated mice exhibit a 5-fold and 15-fold increase in LSK cells and colony-forming unit cells, respectively, in the spleen compared with wild-type mice
• tamoxifen-treated mice exhibit an increased in hematopoietic progenitors compared with wild-type mice
• in a 5-fluorouracil myelosuppression model, tamoxifen-treated mice exhibit increased survival and faster hematologic recovery with less obvious bone marrow regeneration along the endosteal surface and ectopic regeneration in the perisinusoidal space compared with wild-type mice
• tamoxifen-treated mice exhibit hyperproliferation and reduced quiescence of hematopoietic stem/progenitor cells compared with wild-type mice

immune system
• tamoxifen-treated mice exhibit an increase in the percentage of circulating neutrophils compared with wild-type mice
• in the bone marrow of tamoxifen-treated mice


Mouse Genome Informatics
cn87
    Nr1d1tm1.1Rev/Nr1d1tm1.1Rev
Nr1d2tm1.1Rev/Nr1d2tm1.1Rev
Tg(CAG-cre/Esr1*)5Amc/0

involves: BALB/cJ * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice

behavior/neurological
• shortened and fragmented activity period in tamoxifen-treated mice


Mouse Genome Informatics
cn88
    Pmltm1(PML/RARA)Ley/Pml+
Tg(CAG-cre/Esr1*)5Amc/0

involves: BALB/cJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• small decrease in tamoxifen-treated mice
• in one tamoxifen-treated mouse
• hematopoietic stem cells from tamoxifen-treated mice exhibit in vitro self-renewal compared with control cells
• however, tamoxifen-treated mice do not exhibit myeloproliferative disease

immune system
• in one tamoxifen-treated mouse


Mouse Genome Informatics
cn89
    Rfwd2tm1.1Vmd/Rfwd2tm2.1Vmd
Tg(CAG-cre/Esr1*)5Amc/0

involves: C57BL/6 * C57BL/6N * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• xenografted prostate epithelium cells exhibit increased proliferation and form neoplastic prostate structures compared with xenografted wild-type cells (J:172653)

endocrine/exocrine glands
• xenografted prostate epithelium cells exhibit increased proliferation and form neoplastic prostate structures compared with xenografted wild-type cells (J:172653)


Mouse Genome Informatics
cn90
    Aqp2tm1Bxy/Aqp2tm1Bxy
Tg(CAG-cre/Esr1*)5Amc/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after 18 hours of water deprivation, urine osmolality increases from 1860 to 2720 mosmol/ kg water in wild-type mice, but little increase is seen in tamoxifen-treated mutants
• after tamoxifen-induced deletion of Aqp2. osmolality of urine in mutants decreases from ~2000 mosmol/kg water to <500 mosmol/kg water by 4-5 days after tamoxifen injection and remains low at ~ 200 mosmol/kg water

renal/urinary system
• after 18 hours of water deprivation, urine osmolality increases from 1860 to 2720 mosmol/ kg water in wild-type mice, but little increase is seen in tamoxifen-treated mutants
• after tamoxifen-induced deletion of Aqp2. osmolality of urine in mutants decreases from ~2000 mosmol/kg water to <500 mosmol/kg water by 4-5 days after tamoxifen injection and remains low at ~ 200 mosmol/kg water
• dilatation of collecting ducts in the renal cortex and medulla is observed in kidneys 6 weeks after induction resulting from polyuria
• 6 weeks after induction, many kidneys show medullary atrophy
• seen in mice 6 weeks after tamoxifen induction
• seen in mice 6 weeks after tamoxifen induction
• after tamoxifen treatment, mice are severely polyuric, excreting ~10-fold greater fluid than controls


Mouse Genome Informatics
cn91
    Nr2e1tm1Rev/Nr2e1tm1Rev
Tg(CAG-cre/Esr1*)5Amc/?

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• three weeks of voluntary running results in an increased number of dividing cells in the brain
• reduced pool of neural stem cells

behavior/neurological
N
• contextual fear conditioning is normal (J:132664)
• tone-cued memory is normal (J:132664)

cellular
• three weeks of voluntary running results in an increased number of dividing cells in the brain
• reduced pool of neural stem cells


Mouse Genome Informatics
cn92
    Stk3tm1.1Yy/Stk3tm1Yy
Stk4tm1.1Yy/Stk4tm1.1Yy
Tg(CAG-cre/Esr1*)5Amc/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• at 1 - 7 months after tamoxifen treatment

tumorigenesis
• some mice treated with tamoxifen at birth develop cholangiocarcinomas composed of mainly multilayered biliary epithelial cells
• some mice treated with tamoxifen at birth develop cholangiocarcinomas composed of mainly multilayered biliary epithelial cells
• all mice treated with tamoxifen at birth develop tumors which display characteristics of hepatocellular carcinoma by 6 months of age

cardiovascular system
• in some mice at 1 - 7 months after tamoxifen treatment

digestive/alimentary system
• at 1 - 7 months after tamoxifen treatment

hematopoietic system
• in some mice at 1 - 7 months after tamoxifen treatment

immune system
• in some mice at 1 - 7 months after tamoxifen treatment

cellular


Mouse Genome Informatics
cn93
    Kat7tm1.1Avo/Kat7tm1.1Avo
Tg(CAG-cre/Esr1*)5Amc/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
N
• tamoxifen-treated cells exhibit normal cell morphology or excessive cell death (J:170405)


Mouse Genome Informatics
cn94
    Map2k7tm1Rjd/Map2k7tm1Rjd
Tg(CAG-cre/Esr1*)5Amc/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system