Mouse Genome Informatics
hm1
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm1(cre/ERT)Nat
B6.129-Gt(ROSA)26Sortm1(cre/Esr1)Nat
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cn2
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm3(SS18/EGFP)Mrc
involves: 129 * 129S1/Sv * 129X1/SvJ
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 exhibit a dosage and frequency dependent lethality dieing by 16 months unlike in mice lacking cre expression

tumorigenesis
• all mice develop tumors in the juxta-articular region in the limbs with some evidence of calcification
• following tamoxifen treatment, all mice develop tumors in the juxta-articular region in the limbs with some evidence of calcification
• mice develop synovial sarcomas
• following tamoxifen treatment, mice develop synovial sarcomas

Mouse Models of Human Disease
OMIM IDRef(s)
Sarcoma, Synovial 300813 J:147728


Mouse Genome Informatics
cn3
    Gt(ROSA)26Sortm1(CAG-Trp53*,-EGFP)Medz/Gt(ROSA)26Sortm1(cre/ERT)Nat
involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
N
• hematopoietic stem and progenitor cells (HSPCs) of mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA (J:158953)
• the total number of HSPCs is normal in irradiated mice (J:158953)
• following irradiation, the proportion of GFP+ cells in the hematopoietic stem and progenitor cell compartment and myeloid and lymphoid lineages of tamoxifen-treated mice is increased compared to un-irradiated mice
• GFP+ cell accumulation occurs whether mice are treated with tamoxifen 2 or 7 days after irradiation
• however, no competitive advantage is observed when mice are treated with tamoxifen and 5-fluorouracil without DNA damage or over similarly treated Cdkn2atm2.1Rdp cells in irradiated chimera experiments


Mouse Genome Informatics
cn4
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm2(EWSR1/ATF1)Mrc
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system

growth/size
• administration of tamoxifen prior to 3 weeks of age results in stunted growth

mortality/aging
• administration of tamoxifen prior to 3 weeks of age results in death by 12 weeks of age without tumor formation

tumorigenesis
• when tamoxifen is administered after 3 weeks of age more tumors form than without tamoxifen
• tumors most often in extremities, rib cage, and facial tissue
• tumors rare in dermis, liver, and bone
• all mice have tumors by 12 weeks regardless of treatment


Mouse Genome Informatics
cn5
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Pdgfratm12Sor/Pdgfra+

involves: 129 * 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• all tamoxifen-treated mice develop sarcomas of the skin or muscle connective tissue after 10 to 19 weeks
• 2 tamoxifen-treated mice develop large intestinal tumors resembling undifferentiated fibrosarcomas

muscle
• tamoxifen-treated mice develop muscle fibrosis at 10 to 19 weeks of age

integument
• tamoxifen-treated mice develop skin fibrosis at 10 to 19 weeks of age

digestive/alimentary system
• after 15 weeks, tamoxifen-treated mice exhibit intestinal fibrosis


Mouse Genome Informatics
cn6
    Telo2tm1Tdl/Telo2tm1.1Tdl
Trp53tm1Tyj/Trp53tm1Tyj
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129P2/OlaHsd * 129S2/SvPas * C57BL/6J
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 cell cycle arrest after 6 days in culture unlike wild-type cells


Mouse Genome Informatics
cn7
    Aurkatm1.1Tvd/Aurkatm1.1Tvd
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm1Sor

involves: 129 * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• in MEFs at later time points after OHT treatment and serum addition cells develop large aberrant nuclei with frequent micronuclei
• in MEFS after OHT treatment and serum addition increases in the population of cells with 4N and 8N DNA content are seen
• live cell imaging indicates a median 8 h delay in mitotic entry in MEFS after OHT treatment and serum addition compared to controls
• in MEFS after OHT treatment and serum addition more cells are in prophase and most of these show an early prophase phenotype
• in MEFS after OHT treatment and serum addition almost no cells in metaphase, anaphase, and telophase are detected
• in MEFS after OHT treatment and serum addition cells in prometaphase have a monopolar spindle with closely adjacent chromosomes, the presence of these monopolar spindles activates the spindle checkpoint
• in MEFS 28 h after OHT treatment and serum addition the percent of cells positive for PH3 is increased about 3 fold compared to controls
• however, the timing of the peak in PH3 positive cells is similar to controls
• growth defect in MEFs following OHT treatment and serum addition


Mouse Genome Informatics
cn8
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Lhx2tm1Monu/Lhx2tm1Monu

involves: 129 * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
• at E12.5, following tamoxifen treatment at E8.5, mice display an expansion of the cortical hem and a reduction in dorsal telencephalon
• treatment with tamoxifen at E10.5 results in subtle to inapparent abnormalities in the cortical hem at E12.5


Mouse Genome Informatics
cn9
    Droshatm1Litt/Droshatm1.1Litt
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• naive CD4+ T cells release more interferon gamma than controls after cre-mediated deletion of Rnasen induced by tamoxifen treatment
• deficient CD4+ T cells are capable of differentiating into Th1 or Th2 cells


Mouse Genome Informatics
cn10
    Telo2tm1Tdl/Telo2tm1.1Tdl
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129P2/OlaHsd * C57BL/6J
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 decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells
• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) arrest with 2N or 4N DNA content and exhibit reduced S and M phase unlike wild-type MEFs
• after 3 to 4 days in culture tamoxifen-treated mouse embryonic fibroblasts (MEFs) exhibit a flattened senescence-like morphology unlike wild-type MEFs

homeostasis/metabolism
• tamoxifen-treated mouse embryonic fibroblasts exhibit decreased DNA-damage signaling via Trp53, Cdkn1a and Chek1 compared to wild-type cells


Mouse Genome Informatics
cn11
    Aurkatm1.1Tvd/Aurkatm1.1Tvd
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• following injection of tamoxifen at E10.5 most embryonic cells appear to be in prometaphase
• following injection of tamoxifen at E10.5 embryos show a 4 fold increase in PH3 positive cells in the thymus and lungs compared to controls
• following injection of tamoxifen at E10.5 about a 3 fold increase in the percentage of apoptotic cells in the thymus and lungs is seen


Mouse Genome Informatics
cn12
    Acvrl1tm2.1Spo/Acvrl1tm2.1Spo
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• adult mice administered with tamoxifen die 9-21 days after a single injection
• tamoxifen treated females show a shorter survival span than males

growth/size
• tamoxifen treated mutants show signs of illness such as slow movements, weight loss, pale paws, and low pO2 levels from 8-10 days after tamoxifen injection

cardiovascular system
• pulmonary arteries and veins are dilated
• high vascular permeability
• uterus shows signs of arteriovenous malformations in tamoxifen treated mutants
• mutants bearing excisional wounds on the dorsal skin and ear and treated with tamoxifen form arteriovenous shunts in the blood vessels near the wounds
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
• in tamoxifen treated mutants
• in tamoxifen treated mutants
• tamoxifen treated mutants show signs of hemorrhages in the lungs

digestive/alimentary system
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
• tamoxifen treated mutants exhibit darkened feces indicative of the presence of blood

hematopoietic system
• tamoxifen treated mutants exhibit reduced hematocrit
• in tamoxifen treated mutants

respiratory system
• pulmonary arteries and veins are dilated
• high vascular permeability
• tamoxifen treated mutants show signs of hemorrhages in the lungs

Mouse Models of Human Disease
OMIM IDRef(s)
Telangiectasia, Hereditary Hemorrhagic, Type 2; HHT2 600376 J:154620


Mouse Genome Informatics
cn13
    Gt(ROSA)26Sortm1(CAG-Trp53*,-EGFP)Medz/Gt(ROSA)26Sortm1(cre/ERT)Nat
Trp53tm1Tyj/Trp53+

involves: 129 * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
N
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA (J:158953)


Mouse Genome Informatics
cn14
    Gt(ROSA)26Sortm1(CAG-Trp53*,-EGFP)Medz/Gt(ROSA)26Sortm1(cre/ERT)Nat
Trp53tm1Tyj/Trp53tm1Tyj

involves: 129 * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
N
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA (J:158953)


Mouse Genome Informatics
cn15
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu

involves: 129 * 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection

tumorigenesis
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
• 20% of males develop prostate cancer after 4OHT treatment (J:130367)
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment (J:130367)

digestive/alimentary system
• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment

endocrine/exocrine glands
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment (J:130367)

reproductive system
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment (J:130367)
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment (J:130367)

integument
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

homeostasis/metabolism
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively


Mouse Genome Informatics
cn16
    Agr2tm1.1Lpkn/Agr2tm1.1Lpkn
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• in the small intestine and colon following tamoxifen treatment
• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells unlike in wild-type mice
• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
• tamoxifen-treated mice lack normal goblet cells unlike wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice

immune system
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice

endocrine/exocrine glands
• 24 hours following tamoxifen treatment, the Paneth cell compartment is expanded compared to in wild-type mice
• 3 days following tamoxifen treatment, mice show loss of normal goblet cells, acute inflammatory infiltrates in the lamina propria, and further expansion of the Paneth cells compared to in wild-type mice

cellular
• in the small intestine and colon following tamoxifen treatment
• following tamoxifen treatment, enterocyte proliferation in the small intestine and colon is decreased compared to in wild-type mice


Mouse Genome Informatics
cn17
    Atoh1tm3Hzo/Atoh1tm1Hzo
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• after tamoxifen treatment, the external granule cell layer is much thinner than that of control littermates
• after tamoxifen treatment, the layer is depleted of cycling immature precursors


Mouse Genome Informatics
cn18
    Atoh1tm3Hzo/Atoh1tm1Hzo
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm1(Smo/EYFP)Amc

involves: 129 * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• no cycling granule neuron precursor cells are detected in the external granule cell layer 10 days after tamoxifen treatment
• 10 days after tamoxifen treatment
• 10 days after tamoxifen treatment most mice have atrophic cerebella

cellular
• no cycling granule neuron precursor cells are detected in the external granule cell layer 10 days after tamoxifen treatment


Mouse Genome Informatics
cn19
    Atoh1tm3Hzo/Atoh1+
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sortm1(Smo/EYFP)Amc

involves: 129 * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• ectopic masses show numerous mitotic granule neuron precursors 10 days after tamoxifen treatment
• 10 days after tamoxifen treatment, neoplastic and preneoplastic lesions in which the external granule layer lacks the normal layered structure develop in the external layer of the cerebellum
• hypertrophic 10 days after tamoxifen treatment
• 10 days after tamoxifen treatment, neoplastic and preneoplastic lesions in which the external granule layer lacks the normal layered structure develop in the external layer of the cerebellum

cellular
• ectopic masses show numerous mitotic granule neuron precursors 10 days after tamoxifen treatment


Mouse Genome Informatics
cn20
    Gt(ROSA)26Sortm1(CAG-Trp53*,-EGFP)Medz/Gt(ROSA)26Sortm1(cre/ERT)Nat
Tg(H2-K-BCL2)1Josd/0

involves: 129 * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• GFP+ hematopoietic stem and progenitor cells (HSPC) from irradiated mice transplanted into irradiated mice reconstitute the HSPC population exhibit a competitive advantage over HSPC from untreated mice compared with cells from similarly irradiated wild-type mice


Mouse Genome Informatics
cn21
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Pdgfratm12Sor/Pdgfra+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 6 months after tamoxifen treatment, mice develop intestinal disease and eventually die or are sacrificed

digestive/alimentary system
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
• tamoxifen-treated mice exhibit partial or complete fibrosis of the small intestine and cecum unlike in wild-type mice with increased submucosal connective tissue and proportional increase in fibroblast-like cells and collagenous matrix
• in tamoxifen-treated mice

cardiovascular system
• in tamoxifen-treated mice

renal/urinary system
• sclerotic glomeruli in tamoxifen-treated mice
• in tamoxifen-treated mice
• enlarged glomeruli in tamoxifen-treated mice
• in tamoxifen-treated mice

tumorigenesis
• at between 44 and 76 weeks of age, 5 of 29 tamoxifen-treated mice develop sarcomas arising from dermis or muscle connective tissue

muscle
• in tamoxifen-treated mice

respiratory system
• around the bronchioles in tamoxifen-treated mice

integument
• in tamoxifen-treated mice


Mouse Genome Informatics
cn22
    Dnaic1tm1.1Leo/Dnaic1tm1.1Leo
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• following treatment with tamoxifen, cultured tracheal ciliated epithelium exhibits no ciliary activity likely due to a lack of outer dynein arms unlike similarly treated wild-type samples
• however, epithelium morphology and number of ciliated cells are normal following treatment with tamoxifen
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice
• after 3 months, tamoxifen-treated mice exhibit absent mucociliary clearance in the nasopharynx and a 50% decreased in the trachea compared with wild-type mice
• after 6 months, 3 of 4 tamoxifen-treated mice exhibit no mucociliary clearance in the trachea while 1 of 4 mice exhibit a substantial reduction in clearance compared with similarly treated wild-type mice
• after 7.5 months, tamoxifen-treated mice exhibit no mucociliary clearance in the trachea compared with similarly treated wild-type mice

immune system
• tamoxifen-treated mice exhibit chronic rhinosinusitis unlike wild-type mice
• however, no lung inflammation develops in tamoxifen-treated mice

nervous system
N
• despite ciliary defects, tamoxifen-treated mice exhibit no evidence hydroencephaly (J:155730)

Mouse Models of Human Disease
OMIM IDRef(s)
Ciliary Dyskinesia, Primary, 1; CILD1 244400 J:155730


Mouse Genome Informatics
cn23
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Tardbptm1.1Pcw/Tardbptm1.1Pcw

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• when cre expression is induced with a tamoxifen-containing diet (400 mg/kg of chow), mice die by day 9 post-introduction of tamoxifen

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
• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not
• mice show a cumulative loss of body weight compared to controls following cre induction, but energy intake (cumulative food intake) is similar to controls

homeostasis/metabolism
N
• without induction of cre by tamoxifen treatment, animals are indistinguishable from controls (J:164406)
• increased fat oxidation after induction is basis for increased weight loss
• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6

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

cellular
• increased fat oxidation after induction is basis for increased weight loss

behavior/neurological
• energy intake on day 7 is significantly higher than on day 1 after cre induction


Mouse Genome Informatics
cn24
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Tardbptm1.1Pcw/Tardbp+

involves: 129 * C57BL/6 * 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
• during the initial 3 days after cre induction by tamoxifen, all mice show decrease in body weight due to decreased food intake, but whereas controls regain recover some weight, experimental mice do not

homeostasis/metabolism
• following cre induction, animals exhibit a decreased respiratory exchange ratio (RER) indicative of pure fat oxidation compared to controls by day 6

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


Mouse Genome Informatics
cn25
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Ikbkbtm1Lex/Ikbkbtm1Lex

involves: 129S/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• following tamoxifen-treatment, mouse embryonic fibroblasts (MEFs) exhibit impaired chemotaxis in response to HMGB1 compared with wild-type cells
• however, chemotaxis in response to PDGF is normal and chemotaxis is rescued by over expression of Nfkb2
• following tamoxifen-treatment, MEFs exhibit random migration in response to an HMGB1 gradient unlike wild-type cells
• 30 to 60 minutes after exposure to HMGB1, tamoxifen-treated MEFs exhibit reduced migration velocity compared with wild-type mice


Mouse Genome Informatics
cn26
    Gdpd5tm1Itl/Gdpd5tm1.1Itl
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice treated with tamoxifen after neurogenesis (at E10.5) exhibit normal motor pool formation (J:178550)
• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice
• at E12.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti, adductor longus and magnus, and posterior gracilis muscle motor neurons compared with control mice
• at E14.5, mice treated with tamoxifen at E8.5 exhibit fewer Isl1/2+ and vasti muscle motor neurons compared with control mice
• however, motor neurons in adductor longus and magnus and posterior gracilis muscles recover by E14.5

cellular
• mice treated with tamoxifen at E8.5 exhibit delayed motor neuron formation compared with control mice


Mouse Genome Informatics
cn27
    Fzd4tm1Nat/Fzd4tm2.1Nat
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• at E18.5 in mice treated with tamoxifen at E12.5 or E13.5


Mouse Genome Informatics
cn28
    Fzd5tm1Nat/Fzd5tm2Nat
Gt(ROSA)26Sortm1(cre/ERT)Nat/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
nervous system
• PFN in adults displays nearly complete loss of alkaline phosphatase expressing Fzd5-null neurons by 10 days after 4HT injection and cre activation, but no loss is observed in Fzd5tm2Nat/+, cre-positive control PFNs 8 days after 4HT treatment


Mouse Genome Informatics
cn29
    Gpx4tm1.1Qra/Gpx4tm1.1Qra
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die within 2 weeks of the 4th injection of tamoxifen (4 injections administered over an 8 day period)

growth/size
• starting after 3 injections of tamoxifen in mice at 6 - 9 months of age
• becomes significant 1 week after the 4th injection of tamoxifen

cellular
• 1 week after the last tamoxifen injection
• enhanced lipid peroxidation and impaired electron transport chain activity and ATP production in mitochondria 1 week after the last tamoxifen injection

behavior/neurological
• seen in tamoxifen treated mice shortly before death

nervous system
• elevated astrocyte activation in the hippocampal region 1 week after the last tamoxifen injection
• in the hippocampal region 1 week after the last tamoxifen injection

liver/biliary system
• 1 week after the last tamoxifen injection


Mouse Genome Informatics
cn30
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Pdgfratm13Sor/Pdgfra+

involves: 129S4/SvJaeSor * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• 4 of 9 tamoxifen-treated mice exhibit intestinal fibrosis
• in one tamoxifen-treated mouse

renal/urinary system
• sclerotic glomeruli in tamoxifen-treated mice
• enlarged glomeruli in tamoxifen-treated mice

cardiovascular system
• in tamoxifen-treated mice

muscle
• in tamoxifen-treated mice

integument
• in some tamoxifen-treated mice