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/body
• 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/body
• 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/body
• 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/body
• 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
    Pkd1tm2Ggg/Pkd1tm2Ggg
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23


Mouse Genome Informatics
cn28
    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
cn29
    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
cn30
    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/body
• 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
cn31
    Ttc21btm2c(KOMP)Wtsi/Ttc21baln
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

cell line(s): EPD0041_2_E09
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
• levels of cAMP are higher in cystic kidneys of the offspring of E17.5 pregnant females injected with tamoxifen
• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
• elevation in ratio of percent kidney weight to body weight is seen in the offspring of E17.5 pregnant females injected with tamoxifen
• dilations of loops of Henle in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
• dilations of proximal tubules in the kidney cortex are seen by P15 in the offspring of pregnant females injected with tamoxifen at E17.5
• when E17.5 pregnant females are injected intraperitoneally with tamoxifen to induce ubiquitous deletion of Ttc21b, the 6 week old offspring develop cystic kidney disease
• cysts seen in the offspring of E17.5 pregnant females injected with tamoxifen originate from proximal tubules, loops of Henle, and collecting ducts
• 5 week old mice injected intraperitoneally with tamoxifen do not develop kidney cysts after 3 months
• kidneys from offspring of E17.5 pregnant females grown in culture in the presence of 8-bromo-cAMP exhibit increased cystogenic potential and treatment of these cultures with Gant61, a small molecule GLI antagonist, or Sant2, a small molecule SMO antagonist, inhibitors reduces cystogenic potential

homeostasis/metabolism
• increase in BUN levels is seen in the offspring of E17.5 pregnant females injected with tamoxifen

cellular
• kidney primary cilia are stunted and show accumulation of IFT88 protein in bulb-like structures at the distal tips in the offspring of E17.5 pregnant females injected with tamoxifen
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5
• an increase in cell proliferation is seen in kidney tubules of 6-week old offspring from pregnant females injected with tamoxifen at E17.5
• from P15 to P20, an increase in cell proliferation in the renal medulla is seen the offspring of females injected with tamoxifen at E17.5


Mouse Genome Informatics
cn32
    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