Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}
• Allele Name: targeted mutation 3, Alexandra L Joyner
• Allele ID: MGI:5432216
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj	involves: 129S6/SvEvTac * C57BL/6	MGI:5432788
cn2	Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+ Npm1^tm1Trow/Npm1^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Npm1^tm1Trow	MGI:6286134
cn3	Dnmt3a^tm1Trow/Dnmt3a^+ Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+ Npm1^tm1Trow/Npm1^+ Tg(Mx1-cre)1Cgn/0	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Npm1^tm1Trow Dnmt3a^tm1Trow Tg(Mx1-cre)1Cgn	MGI:6286136
cn4	Sftpc^tm1Mfbs/Sftpc^tm1Mfbs Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Sftpc^tm1Mfbs	MGI:8407106
cn5	Sftpc^tm1Mfbs/Sftpc^+ Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Sftpc^tm1Mfbs	MGI:8407107
cn6	Smarce1^tm1Tich/Smarce1^tm2.1Tich Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+ Tg(Cd4-cre)1Cwi/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5474767

Genotype
MGI:5432788

hm1

• Allelic Composition: Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

normal phenotype

no abnormal phenotype detected ( J:186310 )

• mice are viable and fertile with no reported phenotypic abnormalities

Genotype
MGI:6286134

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺; Npm1^tm1Trow/Npm1⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Npm1^tm1Trow

hematopoietic system

abnormal bone marrow hematopoietic cell morphology ( J:272803 )

♀ • increase in total number of colony forming units are found in whole bone marrow cells 4 months post-tamoxifen injection

increased granulocyte monocyte progenitor cell number ( J:272803 )

♀ • expansion of granulocyte and granulocyte-macrophage colony types are found in whole bone marrow cells 4 months post-tamoxifen injection

decreased hematopoietic stem cell number ( J:272803 )

♀ • decrease in frequency and total number of long term hematopoietic stem cells 4 months post-tamoxifen injection

♀ • decrease in total number of short term hematopoietic stem cells 4 months post-tamoxifen injection

abnormal bone marrow cell physiology ( J:272803 )

♀ • bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 29% of animals in a 440 day period due to myeloproliferative disorder

Genotype
MGI:6286136

cn3

• Allelic Composition: Dnmt3a^tm1Trow/Dnmt3a⁺; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺; Npm1^tm1Trow/Npm1⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Npm1^tm1Trow Dnmt3a^tm1Trow Tg(Mx1-cre)1Cgn

hematopoietic system

abnormal bone marrow cell physiology ( J:272803 )

♀ • bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 100% of animals in a 440 day period

♀ • in 33% of mice death is the result of myeloproliferative disorder (MPD)

♀ • in 67% of mice death is the result of mixed myelodysplastic syndrome and myeloproliferative disorder (MDS/MPD)

♀ • bone marrow cells from MDS/MPD or MPD primary transplants transplanted into sublethally irradiated secondary recipients results in 100% lethality due to acute myeloid leukemia (AML)

Genotype
MGI:8407106

cn4

• Allelic Composition: Sftpc^tm1Mfbs/Sftpc^tm1Mfbs; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Sftpc^tm1Mfbs

mortality/aging

decreased survivor rate ( J:267027 )

• tamoxifen-treated mice show decreased survival, with onset of mortality as early as 5 days after induction

• mean survival is lower in males (10.6 days vs. 11.9 days) than in females following tamoxifen treatment

growth/size/body

weight loss ( J:267027 )

• tamoxifen-treated mice exhibit increased weight loss

• tamoxifen-treated mice surviving the acute injury phase show partial recovery from the nadir in body weight

respiratory system

lung inflammation ( J:267027 )

• bilateral pulmonary infiltrates appear, accompanied by increases in BALF protein, peaking at days 7-14 after tamoxifen induction

alveolitis ( J:267027 )

• tamoxifen-treated mice show onset of complex, multiphasic alveolitis

• bronchoalveolar lavage fluid (BALF) from tamoxifen-treated mice shows increases in total cell counts beginning by day 8 and peaking 2 weeks after induction

• BALF shows a complex inflammatory cell prolife after tamoxifen induction, with an early and sustained macrophage accumulation beginning at 7 days, a spike in polymorphonuclear cells (on day 7), and transient alveolar eosinophilia (peak at 2 weeks), and an increase in total lymphocytes by day 7, indicating polycellular alveolitis and diffuse parenchymal damage

abnormal lung morphology ( J:267027 )

• tamoxifen-treated mice develop acute, diffuse lung injury, with time-dependent progression from patchy peribronchial cell infiltrates and interstitial expansion (7 days) to frank parenchymal injury (2 weeks)

• tamoxifen-treated mice show heterogenous parenchymal remodeling with mesenchymal accumulation of alpha-smooth muscle actin-positive cells adjacent to dilated airspaces lined by hyperplastic alveolar type 2 cells at 4-6 weeks after induction

increased type II pneumocyte number ( J:267027 )

• lungs show a 40% persistent increase in alveolar type 2 cell numbers beginning at 7 days after tamoxifen treatment

• however, no significant apoptosis of alveolar type 2 cells is seen after tamoxifen treatment

pulmonary fibrosis ( J:267027 )

• tamoxifen-treated mice surviving the acute lung injury phase develop a fibrotic histological phenotype indicating spontaneous fibrotic lung remodeling

• mice show increased collagen deposition in peripheral lung parenchyma and subpleural regions beginning at 2 weeks after tamoxifen-induction

decreased lung compliance ( J:267027 )

• pressure-volume curves at 4 and 6 weeks following tamoxifen treatment are shifted down (decreased volume with increased pressure) and to the right, with reduced static compliance, indicating restrictive lung physiology

• static compliance, maximally decreased at 4 weeks by 40%, mildly improves at week 6 after tamoxifen-treatment

immune system

lung inflammation ( J:267027 )

• bilateral pulmonary infiltrates appear, accompanied by increases in BALF protein, peaking at days 7-14 after tamoxifen induction

alveolitis ( J:267027 )

• tamoxifen-treated mice show onset of complex, multiphasic alveolitis

• bronchoalveolar lavage fluid (BALF) from tamoxifen-treated mice shows increases in total cell counts beginning by day 8 and peaking 2 weeks after induction

• BALF shows a complex inflammatory cell prolife after tamoxifen induction, with an early and sustained macrophage accumulation beginning at 7 days, a spike in polymorphonuclear cells (on day 7), and transient alveolar eosinophilia (peak at 2 weeks), and an increase in total lymphocytes by day 7, indicating polycellular alveolitis and diffuse parenchymal damage

homeostasis/metabolism

abnormal autophagy ( J:267027 )

• alveolar type II cell lysates from adult mice administered intraperitoneal tamoxifen show an increase in both LC3-II and p62, indicating a late block in macroautophagy, as early as 1 week after tamoxifen induction

hypoxemia ( J:267027 )

• mice exhibit hypoxemia after tamoxifen treatment

cellular

abnormal autophagy ( J:267027 )

• alveolar type II cell lysates from adult mice administered intraperitoneal tamoxifen show an increase in both LC3-II and p62, indicating a late block in macroautophagy, as early as 1 week after tamoxifen induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic pulmonary fibrosis		DOID:0050156		J:267027

Genotype
MGI:8407107

cn5

• Allelic Composition: Sftpc^tm1Mfbs/Sftpc⁺; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Sftpc^tm1Mfbs

respiratory system

alveolitis ( J:267027 )

• adult mice administered intraperitoneal tamoxifen develop moderate alveolitis and interstitial histological changes 2 weeks after induction

immune system

alveolitis ( J:267027 )

• adult mice administered intraperitoneal tamoxifen develop moderate alveolitis and interstitial histological changes 2 weeks after induction

mortality/aging

mortality/aging ( J:267027 )

N • tamoxifen-treated mice do not show early mortality

growth/size/body

growth/size/body region phenotype ( J:267027 )

N • tamoxifen-treated mice do not show weight loss

Genotype
MGI:5474767

cn6

• Allelic Composition: Smarce1^tm1Tich/Smarce1^tm2.1Tich; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

immune system

immune system phenotype ( J:194195 )

N • tamoxifen-treated mice exhibit no gross functional defects in mature T cells