Phenotypes associated with this allele

• Allele Symbol: Tgfbr2^tm1.2Hlm
• Allele Name: targeted mutation 1.2, Harold L Moses
• Allele ID: MGI:2384513
• Summary: 21 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm	involves: 129S6/SvEvTac * C57BL/6	MGI:2386218
cn2	Kras^tm4Tyj/Kras^+ Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm	B6.129-Kras^tm4Tyj Tgfbr2^tm1.2Hlm	MGI:5304695
cn3	Hprt1^tm1(CAG-Tgfbr1*)Lba/Y Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0	involves: 129 * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3846745
cn4	Hprt1^tm1(CAG-Tgfbr1*)Lba/Hprt1^tm1(CAG-Tgfbr1*)Lba Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0	involves: 129 * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3846748
cn5	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2 * NOD	MGI:5514240
cn6	Ifng^tm1Ts/Ifng^tm1Ts Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0 Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514242
cn7	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514241
cn8	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tnfrsf4^tm2(cre)Nik/Tnfrsf4^+ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129 * C57BL/6 * NOD * SJL	MGI:5514245
cn9	Kras^tm4Tyj/Kras^+ Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Ptf1a^tm1.1(cre)Cvw/Ptf1a^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3695567
cn10	Kras^tm4Tyj/Kras^+ Tgfbr2^tm1.2Hlm/Tgfbr2^+ Ptf1a^tm1.1(cre)Cvw/Ptf1a^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3695569
cn11	Ptf1a^tm1.1(cre)Cvw/Ptf1a^+ Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3695570
cn12	Tg(CAG-cre/Esr1*)5Amc/0 Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5688888
cn13	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Col1a2-cre/ERT,-ALPP)7Cpd/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5543401
cn14	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3846755
cn15	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5523280
cn16	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S6/SvEvTac * C57BL/6J * CBA/J	MGI:3623395
cn17	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(KRT14-cre)52Smr/0	involves: 129S6/SvEvTac * C57BL/6J * SJL/J	MGI:5300942
cn18	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(CD207-cre)1Dhka/?	involves: 129S6/SvEvTac * C57BL/6J * SJL/J	MGI:3761678
cn19	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Foxp3-EGFP/cre)1cJbs/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129S6/SvEvTac * C57BL/6 * NOD * SJL	MGI:5514247
cn20	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Acvrl1-cre)L1Spo/0	involves: 129S6/SvEvTac * FVB/N	MGI:4398920
cn21	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Twist2^tm1(cre)Dor/Twist2^+	involves: 129X1/SvJ * C57BL/6	MGI:4943503

Genotype
MGI:2386218

hm1

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm
• 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:75073 )

neoplasm

neoplasm ( J:177379 )

N • mutants with an intranasal instillation of an adenovirus expressing cre recombinase do not develop any discernable tumors over a 10-week period

Genotype
MGI:5304695

cn2

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm
• Genetic Background: B6.129-Kras^tm4Tyj Tgfbr2^tm1.2Hlm

mortality/aging

premature death ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 43 days

neoplasm

increased metastatic potential ( J:177379 )

• tumors of Cre adenoviral treated mutants show transmural invasion of vessels and pleural invasion, and regional metastases to mediastinal lymph nodes

increased lung adenocarcinoma incidence ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop tumors similar to human mixed subtype adenocarcinomas; they show progression of a pure noninvasive lung adenocarcinoma to an adenocarcinoma with mixed invasive morphology and metastatic potential

• tumors of mutants treated with Cre adenovirus show evidence of inflammatory cell recruitment and tumor microenvironment remodeling with neoangiogenesis not seen in homozygous cre adenovirus treated Kras^tm4Tyj mice

hematopoietic system

increased B cell number ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Kras^tm4Tyj mice

increased T cell number ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Kras^tm4Tyj mice

abnormal myeloid leukocyte morphology ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls

immune system

increased B cell number ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Kras^tm4Tyj mice

increased T cell number ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Kras^tm4Tyj mice

abnormal myeloid leukocyte morphology ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls

respiratory system

increased lung adenocarcinoma incidence ( J:177379 )

• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop tumors similar to human mixed subtype adenocarcinomas; they show progression of a pure noninvasive lung adenocarcinoma to an adenocarcinoma with mixed invasive morphology and metastatic potential

• tumors of mutants treated with Cre adenovirus show evidence of inflammatory cell recruitment and tumor microenvironment remodeling with neoangiogenesis not seen in homozygous cre adenovirus treated Kras^tm4Tyj mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung cancer		DOID:1324	OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210	J:177379

Genotype
MGI:3846745

cn3

• Allelic Composition: Hprt1^{tm1(CAG-Tgfbr1*)Lba}/Y; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6 * DBA/2

immune system

immune system phenotype ( J:148747 )

♂N • these mice do not have the wasting autoimmune disease normally observed in mice with conditional deletion of Tgfbr2 in CD4⁺ T cells

Genotype
MGI:3846748

cn4

• Allelic Composition: Hprt1^{tm1(CAG-Tgfbr1*)Lba}/Hprt1^{tm1(CAG-Tgfbr1*)Lba}; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * 129S6/SvEvTac * C57BL/6 * DBA/2

immune system

immune system phenotype ( J:148747 )

♀N • these mice do not have the wasting autoimmune disease normally observed in mice with conditional deletion of Tgfbr2 in CD4⁺ T cells

Genotype
MGI:5514240

cn5

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD

mortality/aging

premature death ( J:196160 )

• die at 3-4 weeks of age, before hyperglycemia is seen

immune system

increased inflammatory response ( J:196160 )

• severe inflammatory infiltration of multiple organs

Genotype
MGI:5514242

cn6

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

mortality/aging

mortality/aging ( J:196160 )

N • improved survival

immune system

immune system phenotype ( J:196160 )

N • do not develop diabetes

Genotype
MGI:5514241

cn7

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

mortality/aging

mortality/aging ( J:196160 )

N • improved survival

immune system

immune system phenotype ( J:196160 )

N • absolute numbers of Th1 cells in the spleen is unchanged from controls

abnormal immune system morphology ( J:196160 )

decreased regulatory T cell number ( J:196160 )

• significant reduction in spleen and pancreas

• reduced peripheral cell numbers

increased regulatory T cell number ( J:196160 )

• percentage in pancreatic lymph nodes is increased

abnormal immune system organ morphology ( J:196160 )

abnormal spleen morphology ( J:196160 )

• total cellularity of the spleen is reduced in 3 week old diabetic mice

abnormal abdominal lymph node morphology ( J:196160 )

• total cellularity of pancreatic lymph nodes is reduced in 3 week old diabetic mice

abnormal immune system physiology ( J:196160 )

pancreas inflammation ( J:196160 )

• massive infiltration of leukocytes into Islets before diabetes develops

abnormal immune serum protein physiology ( J:196160 )

increased interferon-gamma secretion ( J:196160 )

• in pancreatic T cells

abnormal interleukin secretion ( J:196160 )

• decreased Il22 expression in pancreatic T cells

decreased interleukin-17 secretion ( J:196160 )

• decreased Il17a in pancreatic T cells

increased interleukin-2 secretion ( J:196160 )

• in pancreatic T cells

increased interleukin-21 secretion ( J:196160 )

• in pancreatic T cells

decreased interleukin-9 secretion ( J:196160 )

• in pancreatic T cells

increased susceptibility to autoimmune diabetes ( J:196160 )

• become diabetic between 14 and 21 days of age

endocrine/exocrine glands

pancreas inflammation ( J:196160 )

• massive infiltration of leukocytes into Islets before diabetes develops

hematopoietic system

decreased regulatory T cell number ( J:196160 )

• significant reduction in spleen and pancreas

• reduced peripheral cell numbers

increased regulatory T cell number ( J:196160 )

• percentage in pancreatic lymph nodes is increased

abnormal spleen morphology ( J:196160 )

• total cellularity of the spleen is reduced in 3 week old diabetic mice

Genotype
MGI:5514245

cn8

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129 * C57BL/6 * NOD * SJL

immune system

immune system phenotype ( J:196160 )

N • absolute number of T reg cells in the spleen and the pancreatic lymph nodes are normal

increased susceptibility to autoimmune diabetes ( J:196160 )

• development of diabetes is somewhat delayed

Genotype
MGI:3695567

cn9

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Ptf1a^{tm1.1(cre)Cvw}/Ptf1a⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

premature death ( J:116129 )

• some die suddenly with a median survival of 59 days

growth/size/body

weight loss ( J:116129 )

distended abdomen ( J:116129 )

• begin to demonstrate abdominal distension at around 6-7 weeks of age due to pancreatic tumor

enlarged spleen ( J:116129 )

• seen frequently

neoplasm

increased pancreas tumor incidence ( J:116129 )

• 100% penetrance of pancreatic tumors

increased pancreatic ductal adenocarcinoma incidence ( J:116129 )

• progressive development of pancreatic ductal adenocarcinoma; tumor uniformly occupies the whole pancreas and is irregularly shaped and results in almost complete loss of normal pancreatic tissue

• carcinoma cells frequently show nuclear atypia and invasion beyond the basement membrane

• stromal expansion starts in the early tumorigenesis stages and tumors do not show sarcomatoid architecture

• 100% penetrance and tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions

increased pancreatic intraepithelial neoplasia incidence ( J:116129 )

• tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions

increased metastatic potential ( J:116129 )

• although no distant metastasis is seen at 7-10 weeks of age, the few mutants that survive up to 24-27 weeks, show prominent desmoplasia and liver metastasis, lung metastasis, diaphragmatic and duodenal invasion and peritoneal dissemination

liver/biliary system

dilated gallbladder ( J:116129 )

• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation

hepatic necrosis ( J:116129 )

• at late-stage tumor burden, exhibit multiple necrotic areas in the distal liver parenchyma

jaundice ( J:116129 )

• observed sometimes

homeostasis/metabolism

abnormal hepatic portal vein thrombosis ( J:116129 )

• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus

hemorrhagic ascites ( J:116129 )

• frequently display bloody ascites

hematopoietic system

enlarged spleen ( J:116129 )

• seen frequently

immune system

enlarged spleen ( J:116129 )

• seen frequently

behavior/neurological

paralysis ( J:116129 )

• a few mutants exhibit paraplegia, most likely because of circulation failure due to oppression of large vessels by the growing tumor

digestive/alimentary system

abnormal duodenum morphology ( J:116129 )

• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation

endocrine/exocrine glands

dilated gallbladder ( J:116129 )

• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation

increased pancreas tumor incidence ( J:116129 )

• 100% penetrance of pancreatic tumors

increased pancreatic ductal adenocarcinoma incidence ( J:116129 )

• progressive development of pancreatic ductal adenocarcinoma; tumor uniformly occupies the whole pancreas and is irregularly shaped and results in almost complete loss of normal pancreatic tissue

• carcinoma cells frequently show nuclear atypia and invasion beyond the basement membrane

• stromal expansion starts in the early tumorigenesis stages and tumors do not show sarcomatoid architecture

• 100% penetrance and tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions

increased pancreatic intraepithelial neoplasia incidence ( J:116129 )

• tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions

cardiovascular system

abnormal hepatic portal vein morphology ( J:116129 )

• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus

Genotype
MGI:3695569

cn10

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tgfbr2^tm1.2Hlm/Tgfbr2⁺; Ptf1a^{tm1.1(cre)Cvw}/Ptf1a⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

premature death ( J:116129 )

• exhibit reduced survival than controls after 200 days of age, with a median survival of 347 days

neoplasm

increased pancreas tumor incidence ( J:116129 )

• pancreatic tumors examined demonstrate a dominant sarcomatoid histology (50% or more) as well as the ductal adenocarcinoma

increased pancreatic ductal adenocarcinoma incidence ( J:116129 )

• at 200 days of age or later, show well-differentiated ductal adenocarcinoma in the pancreas head region

increased pancreatic intraepithelial neoplasia incidence ( J:116129 )

• develop pancreatic intraepithelial neoplasia (mPanIN) lesions predominantly in the pancreas tail region

increased metastatic potential ( J:116129 )

• tumors frequently show gross metastasis to the liver and lung, direct invasion to the duodenum, and also peritoneal dissemination

• frequency of metastasis or invasion is much higher (about 50%) than in similar mutants with homozygous, instead of heterozygous, loss of Tgfbr2

endocrine/exocrine glands

increased pancreas tumor incidence ( J:116129 )

• pancreatic tumors examined demonstrate a dominant sarcomatoid histology (50% or more) as well as the ductal adenocarcinoma

increased pancreatic ductal adenocarcinoma incidence ( J:116129 )

• at 200 days of age or later, show well-differentiated ductal adenocarcinoma in the pancreas head region

increased pancreatic intraepithelial neoplasia incidence ( J:116129 )

• develop pancreatic intraepithelial neoplasia (mPanIN) lesions predominantly in the pancreas tail region

Genotype
MGI:3695570

cn11

• Allelic Composition: Ptf1a^{tm1.1(cre)Cvw}/Ptf1a⁺; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * DBA/2

endocrine/exocrine glands

abnormal pancreas development ( J:116129 )

• somatostatin-positive cells are more frequently observed at 1 day of age and at 7 weeks of age, however this difference disappears by 12 weeks of age and the pancreas appears very normal, indicating only subtle effects on pancreas development

Genotype
MGI:5688888

cn12

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

cardiovascular system

abnormal retina vasculature morphology ( J:221181 )

• the capillary network of the intermediate and deep plexus is denser in tamoxifen treated mutants than in controls

• retinal capillaries of tamoxifen treated mice are surrounded by 1-2 complete layers of smooth muscle-like cells that are completely surrounded by a basal lamina that is thicker than in controls compared to controls in which pericytes share the basal lamina with endothelial cells

• marker analysis indicates endothelial cell loss in the retinal vasculature of tamoxifen treated mice

• proliferative retinopathy in tamoxifen treated mice results in the formation of epiretinal vascular membranes on the surface of the retina that are not seen in controls

abnormal retina blood vessel morphology ( J:221181 )

• dilation of retinal vessels and tortuous vessels with massive vascular leakage are seen in tamoxifen treated mice at 4 weeks of age

• retinal vessels of tamoxifen treated mice show the presence of numerous caveolae along the luminal cell membrane of their endothelial cells

• many capillaries in the outer plexiform layer show a narrowed or absent lumen and the opposing vascular walls of capillaries are often in contact with each other in tamoxifen treated mice

retina microaneurysm ( J:221181 )

• capillary microaneurysms are seen in close association with retinal capillaries throughout the retina of tamoxifen treated mice

• microaneurysms originate laterally from capillaries or are localized at the blind-ending tips of capillaries, have a wide lumen frequently filled with erythrocytes, and are found in capillaries form all three (superficial, intermediate, and deep) vascular plexus of the retina

retina neovascularization ( J:221181 )

• retina shows neovascularization into the vitreous of tamoxifen treated mice

abnormal pericyte morphology ( J:221181 )

• retinal capillaries of tamoxifen treated mice are not covered by differentiated pericytes but by a coat of vascular smooth muscle-like cells, indicating lack of pericyte differentiation

retina hemorrhage ( J:221181 )

• accumulations of erythrocytes between perikarya of retina neurons are seen in tamoxifen treated mutants, indicating intraretinal hemorrhage

• regional hemorrhages are seen between photoreceptor outer segments and cells of the retinal pigment epithelium of tamoxifen treated mice

vitreous body hemorrhage ( J:221181 )

• in tamoxifen treated mice

vision/eye

vitreous body hemorrhage ( J:221181 )

• in tamoxifen treated mice

increased retina apoptosis ( J:221181 )

• increase in neuronal apoptotic cell death in the retina of tamoxifen treated mice

persistence of hyaloid vascular system ( J:221181 )

• hyaloid vessels are still detectable in 8 week old tamoxifen treated mice, indicating persistence of the hyaloid vasculature

abnormal retina morphology ( J:221181 )

• tamoxifen treated mice show numerous white areas on the retina which form fluffy white patches or are dot-like at 8 weeks of age and look like hard exudates and cotton wool spots seen in humans with diabetic retinopathy

• tamoxifen treated mice show capillaries that penetrate the inner limiting membrane of the retina and grow into the vitreous body to cause proliferative retinopathy at about 6 weeks of age

abnormal retina vasculature morphology ( J:221181 )

• the capillary network of the intermediate and deep plexus is denser in tamoxifen treated mutants than in controls

• retinal capillaries of tamoxifen treated mice are surrounded by 1-2 complete layers of smooth muscle-like cells that are completely surrounded by a basal lamina that is thicker than in controls compared to controls in which pericytes share the basal lamina with endothelial cells

• marker analysis indicates endothelial cell loss in the retinal vasculature of tamoxifen treated mice

• proliferative retinopathy in tamoxifen treated mice results in the formation of epiretinal vascular membranes on the surface of the retina that are not seen in controls

abnormal retina blood vessel morphology ( J:221181 )

• dilation of retinal vessels and tortuous vessels with massive vascular leakage are seen in tamoxifen treated mice at 4 weeks of age

• retinal vessels of tamoxifen treated mice show the presence of numerous caveolae along the luminal cell membrane of their endothelial cells

• many capillaries in the outer plexiform layer show a narrowed or absent lumen and the opposing vascular walls of capillaries are often in contact with each other in tamoxifen treated mice

retina microaneurysm ( J:221181 )

• capillary microaneurysms are seen in close association with retinal capillaries throughout the retina of tamoxifen treated mice

• microaneurysms originate laterally from capillaries or are localized at the blind-ending tips of capillaries, have a wide lumen frequently filled with erythrocytes, and are found in capillaries form all three (superficial, intermediate, and deep) vascular plexus of the retina

retina neovascularization ( J:221181 )

• retina shows neovascularization into the vitreous of tamoxifen treated mice

retina hemorrhage ( J:221181 )

• accumulations of erythrocytes between perikarya of retina neurons are seen in tamoxifen treated mutants, indicating intraretinal hemorrhage

• regional hemorrhages are seen between photoreceptor outer segments and cells of the retinal pigment epithelium of tamoxifen treated mice

abnormal retina layer morphology ( J:221181 )

• tamoxifen treated mice show loss of the layered structure of the sensory retina

abnormal retina neuronal layer morphology ( J:221181 )

• tamoxifen treated mice show loss of retinal neurons

decreased retina ganglion cell number ( J:221181 )

• tamoxifen treated mice show reduced retinal ganglion cell numbers

thin retina outer nuclear layer ( J:221181 )

• thickness of the outer nuclear layer is reduced in tamoxifen treated mice

retina detachment ( J:221181 )

• 4 month old mice treated with tamoxifen often exhibit detachment of the sensory retina which remains in contact with the underlying retinal pigment epithelium by thin strands of presumably glial tissue

abnormal electroretinogram waveform feature ( J:221181 )

• tamoxifen treated mice show a reduction in b-wave/a-wave amplitude ratio that indicates a more pronounced inner retinal function loss

decreased a-wave amplitude ( J:221181 )

• in tamoxifen treated mice

decreased b-wave amplitude ( J:221181 )

• in tamoxifen treated mice

hematopoietic system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

homeostasis/metabolism

hypoxia ( J:221181 )

• marker analysis indicates retinal hypoxia in tamoxifen treated mice

immune system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

nervous system

microgliosis ( J:221181 )

• retinal capillaries are surrounded by reactive microglial cells in tamoxifen treated mice

decreased retina ganglion cell number ( J:221181 )

• tamoxifen treated mice show reduced retinal ganglion cell numbers

cellular

increased retina apoptosis ( J:221181 )

• increase in neuronal apoptotic cell death in the retina of tamoxifen treated mice

Genotype
MGI:5543401

cn13

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Col1a2-cre/ERT,-ALPP)7Cpd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

neoplasm

increased prostate gland adenocarcinoma incidence ( J:204736 )

♂ • focal areas of prostate adenocarcinomas are seen by 17 weeks of age in tamoxifen treated mice and these areas of adenocarcinoma expand throughout the life of mutants

♂ • prostates exhibit no regression acutely after castration, indicating castrate-resistant prostate cancer

♂ • administration of Sabutoclax (Bl-97C1), a pan-active Bcl2 protein family antagonist, mediates apoptosis in castrate-resistant prostate cancer cells of 36-week old mutant mice and reduces tumor size, however it has little apoptotic effect on benign prostate tissue

increased prostate intraepithelial neoplasia incidence ( J:204736 )

♂ • tamoxifen treated mice develop prostatic intraepithelial neoplasia (PIN) lesions in the prostate by 17 weeks of age, throughout each of the anterior and dorsolateral lobes with 100% penetrance

reproductive system

increased prostate gland adenocarcinoma incidence ( J:204736 )

♂ • focal areas of prostate adenocarcinomas are seen by 17 weeks of age in tamoxifen treated mice and these areas of adenocarcinoma expand throughout the life of mutants

♂ • prostates exhibit no regression acutely after castration, indicating castrate-resistant prostate cancer

♂ • administration of Sabutoclax (Bl-97C1), a pan-active Bcl2 protein family antagonist, mediates apoptosis in castrate-resistant prostate cancer cells of 36-week old mutant mice and reduces tumor size, however it has little apoptotic effect on benign prostate tissue

increased prostate intraepithelial neoplasia incidence ( J:204736 )

♂ • tamoxifen treated mice develop prostatic intraepithelial neoplasia (PIN) lesions in the prostate by 17 weeks of age, throughout each of the anterior and dorsolateral lobes with 100% penetrance

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:204736 )

♂ • focal areas of prostate adenocarcinomas are seen by 17 weeks of age in tamoxifen treated mice and these areas of adenocarcinoma expand throughout the life of mutants

♂ • prostates exhibit no regression acutely after castration, indicating castrate-resistant prostate cancer

♂ • administration of Sabutoclax (Bl-97C1), a pan-active Bcl2 protein family antagonist, mediates apoptosis in castrate-resistant prostate cancer cells of 36-week old mutant mice and reduces tumor size, however it has little apoptotic effect on benign prostate tissue

increased prostate intraepithelial neoplasia incidence ( J:204736 )

♂ • tamoxifen treated mice develop prostatic intraepithelial neoplasia (PIN) lesions in the prostate by 17 weeks of age, throughout each of the anterior and dorsolateral lobes with 100% penetrance

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:204736

Genotype
MGI:3846755

cn14

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

mortality/aging

postnatal lethality, complete penetrance ( J:148747 )

• mice die by three weeks of age from a rampant wasting autoimmune disease

immune system

abnormal T cell activation ( J:148747 )

• more T cells in these mice are in an activated state with CD69 and CD44 upregulated and CD62L downregulated

autoimmune response ( J:148747 )

• mice suffer from a generalized autoimmune disease

liver inflammation ( J:148747 )

• liver inflammation occurs in these mice before death

• portal tracts are enlarged, contain congested vessels, and are infiltrated by numerous lymphocytes

liver/biliary system

liver inflammation ( J:148747 )

• liver inflammation occurs in these mice before death

• portal tracts are enlarged, contain congested vessels, and are infiltrated by numerous lymphocytes

hematopoietic system

abnormal T cell activation ( J:148747 )

• more T cells in these mice are in an activated state with CD69 and CD44 upregulated and CD62L downregulated

Genotype
MGI:5523280

cn15

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:164749 )

N • treatment of mice with oral dose of 160 mg/kg BW per day raloxifene for 21 days resulted in similar recombinase activity as the tamoxifen regimen, but does not cause any cardiac dysfunction; lower (20 mg/kg BW) oral tamoxifen treatment for 21 days does not cause dysfunction

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

mortality/aging

premature death ( J:164749 )

• by 6 days following IP tamoxifen treatment (80 mg/kg BW for 5 days), 60% mortality of treated mice is observed

muscle

dilated cardiomyopathy ( J:164749 )

• mice die by 6 days post-treatment (80 mg/kg BW IP for 5 days) from severe dilated cardiomyopathy

• oral delivery of 80 mg/kg BW tamoxifen for 7 days does not result in any mortality but treated mice exhibit a significant but reversible dilated cardiomyopathy

decreased cardiac muscle contractility ( J:164749 )

• 3 days after oral tamoxifen treatment, cardiac depression peaks with fractional shortening decreasing from 61 to 27% and end-diastolic dimension increasing significantly

Genotype
MGI:3623395

cn16

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CBA/J

mortality/aging

postnatal lethality, complete penetrance ( J:104325 )

• lethality in the immediate postnatal period

cardiovascular system

abnormal dorsal aorta morphology ( J:104325 )

• the dorsal aorta is supplied soley via the ductus arteriosus

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

abnormal aortic arch morphology ( J:104325 )

retroesophageal right subclavian artery ( J:104325 )

• 5/17 have a right subclavian artery that originates retroesophageally from the dorsal aorta

interrupted aortic arch, type b ( J:104325 )

• E12.5 or older embryos have an interruption of the aortic arch between the left carotid artery and the left subclavian artery (IAA type B)

persistent truncus arteriosus ( J:104325 )

• all E12.5 or older embryos exhibit persistent truncus arteriosus, specifically subtype PTA-A4, resulting from a failure in the formation of the aorticopulmonary (A/P) septum

• the ascending aorta branches into the carotid arteries but does not connect to the dorsal aorta, and the dorsal aorta is supplied soley via the ductus arteriosus

ventricular septal defect ( J:104325 )

• ventricular septum defect

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

abnormal cranium morphology ( J:86042 )

• show severe skull defects at birth

small cranium ( J:86042 )

• skull is about 25% smaller than in wild-type

abnormal neurocranium morphology ( J:86042 )

• calvaria development is impaired

absent frontal bone ( J:86042 )

• missing at birth

abnormal parietal bone morphology ( J:86042 )

• induction of parietal bone development fails to occur at E16.5

• severely retarded parietal bone at birth

abnormal mandible morphology ( J:86042 )

absent mandibular angle ( J:86042 )

• at birth shows a missing mandibular angle

small mandibular condyloid process ( J:86042 )

• at birth shows a reduction in the condyle

small mandibular coronoid process ( J:86042 )

• at birth shows a reduction in the coronoid process

small mandible ( J:86042 )

• mandible is smaller at birth

small maxilla ( J:86042 )

• maxilla is smaller at birth

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate

nervous system

abnormal brain dura mater morphology ( J:86042 )

• dura mater development is severely impaired at E14.5, with embryos showing a single cell layer that is poorly developed

skeleton

abnormal cranium morphology ( J:86042 )

• show severe skull defects at birth

small cranium ( J:86042 )

• skull is about 25% smaller than in wild-type

abnormal neurocranium morphology ( J:86042 )

• calvaria development is impaired

absent frontal bone ( J:86042 )

• missing at birth

abnormal parietal bone morphology ( J:86042 )

• induction of parietal bone development fails to occur at E16.5

• severely retarded parietal bone at birth

abnormal mandible morphology ( J:86042 )

absent mandibular angle ( J:86042 )

• at birth shows a missing mandibular angle

small mandibular condyloid process ( J:86042 )

• at birth shows a reduction in the condyle

small mandibular coronoid process ( J:86042 )

• at birth shows a reduction in the coronoid process

small mandible ( J:86042 )

• mandible is smaller at birth

small maxilla ( J:86042 )

• maxilla is smaller at birth

embryo

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

decreased cranial neural crest cell proliferation ( J:86042 )

• cranial neural crest (CNC) cell proliferation activity is severely impaired at E14.5, however no defect in CNC migration

digestive/alimentary system

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate

cellular

decreased cranial neural crest cell proliferation ( J:86042 )

• cranial neural crest (CNC) cell proliferation activity is severely impaired at E14.5, however no defect in CNC migration

muscle

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

growth/size/body

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate

Genotype
MGI:5300942

cn17

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(KRT14-cre)52Smr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL/J

behavior/neurological

absent gastric milk in neonates ( J:112634 )

• animals lack milk in their stomachs

mortality/aging

neonatal lethality ( J:112634 )

• animals die shortly after birth

craniofacial

abnormal palate development ( J:112634 )

• BrdU incorporation analysis indicated that there was no defect of cell proliferation in the palatal mesenchyme of the mutant mice

abnormal primary palate development ( J:112634 )

• the primary palate failed to extend backward and to fuse with the secondary palatal shelves; instead, elevated epithelial cell proliferation activity resulted in the formation of an epithelial tongue, which prevented the fusion between primary and secondary palate

abnormal palatal shelf morphology ( J:112634 )

• on the secondary palatal shelves, a shining transparent strip was located on the posterior part of midline

abnormal palatal shelf fusion at midline ( J:112634 )

• a persistent midline epithelial seam was located in the anterior part of the secondary palate and formed a cyst

• an epithelial bridge separated palatine bone and prevented fusion in the midline

• at E14.5, apoptotic cells were found in the medial edge seam at anterior, middle and posterior region of the developing palate, particularly in the nasal and oral epithelial triangles in wild-type samples, but, no apoptotic positive cells were detected in the medial edge seam in the anterior, middle and posterior region of palate in mutant samples

• at E14.5, medial edge epithelial cells in the mutant palate still maintained the ability to proliferate throughout the entire palate, as measured by BrdU incorporation, and prevented palatal fusion in the middle and posterior part of the mutant palate sample, while there was no proliferation activity in the MEE of the wild-type sample

abnormal hard palate morphology ( J:112634 )

• a transversal section showed that the muscle attachments were misdirected anteriorly and attached onto the posterior portion of the bony palate, a typical malformation of the submucous cleft

abnormal soft palate morphology ( J:208431 )

• cell proliferation is reduced in the soft palate at E14.5 and E15.5, however apoptosis is unaffected

abnormal soft palate muscle morphology ( J:208431 )

• total volume of muscle in the soft palate is reduced at E15.5

small levator veli palatini muscle ( J:208431 )

• levator veli palatini muscle is reduced in volume and is smaller in newborns

small tensor veli palatini muscle ( J:208431 )

• tensor veli palatini is reduced in volume and is smaller in newborns

cleft secondary palate ( J:112634 )

• a complete cleft was manifested in the posterior part of the soft palate

cleft soft palate ( J:208431 )

• 100% of mice develop cleft soft palate, with cleft seen from E15.5 onwards

abnormal nasal septum morphology ( J:112634 )

• the nasal septum failed to fuse with the palatal shelves

digestive/alimentary system

abnormal palate development ( J:112634 )

• BrdU incorporation analysis indicated that there was no defect of cell proliferation in the palatal mesenchyme of the mutant mice

abnormal primary palate development ( J:112634 )

• the primary palate failed to extend backward and to fuse with the secondary palatal shelves; instead, elevated epithelial cell proliferation activity resulted in the formation of an epithelial tongue, which prevented the fusion between primary and secondary palate

abnormal palatal shelf morphology ( J:112634 )

• on the secondary palatal shelves, a shining transparent strip was located on the posterior part of midline

abnormal palatal shelf fusion at midline ( J:112634 )

• a persistent midline epithelial seam was located in the anterior part of the secondary palate and formed a cyst

• an epithelial bridge separated palatine bone and prevented fusion in the midline

• at E14.5, apoptotic cells were found in the medial edge seam at anterior, middle and posterior region of the developing palate, particularly in the nasal and oral epithelial triangles in wild-type samples, but, no apoptotic positive cells were detected in the medial edge seam in the anterior, middle and posterior region of palate in mutant samples

• at E14.5, medial edge epithelial cells in the mutant palate still maintained the ability to proliferate throughout the entire palate, as measured by BrdU incorporation, and prevented palatal fusion in the middle and posterior part of the mutant palate sample, while there was no proliferation activity in the MEE of the wild-type sample

abnormal hard palate morphology ( J:112634 )

• a transversal section showed that the muscle attachments were misdirected anteriorly and attached onto the posterior portion of the bony palate, a typical malformation of the submucous cleft

abnormal soft palate morphology ( J:208431 )

• cell proliferation is reduced in the soft palate at E14.5 and E15.5, however apoptosis is unaffected

abnormal soft palate muscle morphology ( J:208431 )

• total volume of muscle in the soft palate is reduced at E15.5

small levator veli palatini muscle ( J:208431 )

• levator veli palatini muscle is reduced in volume and is smaller in newborns

small tensor veli palatini muscle ( J:208431 )

• tensor veli palatini is reduced in volume and is smaller in newborns

cleft secondary palate ( J:112634 )

• a complete cleft was manifested in the posterior part of the soft palate

cleft soft palate ( J:208431 )

• 100% of mice develop cleft soft palate, with cleft seen from E15.5 onwards

respiratory system

abnormal nasal septum morphology ( J:112634 )

• the nasal septum failed to fuse with the palatal shelves

muscle

abnormal soft palate muscle morphology ( J:208431 )

• total volume of muscle in the soft palate is reduced at E15.5

small levator veli palatini muscle ( J:208431 )

• levator veli palatini muscle is reduced in volume and is smaller in newborns

small tensor veli palatini muscle ( J:208431 )

• tensor veli palatini is reduced in volume and is smaller in newborns

abnormal skeletal muscle fiber morphology ( J:208431 )

• muscle fibers are aligned in the anterior-posterior direction in the soft palate in contrast to the lateral-medial alignment in controls

• muscles are attached to the posterior border of the hard palate

• myofibers in the soft palate are thin and disorganized, appearing wavy and lacking striation, and are decreased in diameter

centrally nucleated skeletal muscle fibers ( J:208431 )

• percentage of centrally placed nuclei in soft palate myofibers is increased

growth/size/body

abnormal palate development ( J:112634 )

• BrdU incorporation analysis indicated that there was no defect of cell proliferation in the palatal mesenchyme of the mutant mice

abnormal primary palate development ( J:112634 )

• the primary palate failed to extend backward and to fuse with the secondary palatal shelves; instead, elevated epithelial cell proliferation activity resulted in the formation of an epithelial tongue, which prevented the fusion between primary and secondary palate

abnormal palatal shelf morphology ( J:112634 )

• on the secondary palatal shelves, a shining transparent strip was located on the posterior part of midline

abnormal palatal shelf fusion at midline ( J:112634 )

• a persistent midline epithelial seam was located in the anterior part of the secondary palate and formed a cyst

• an epithelial bridge separated palatine bone and prevented fusion in the midline

• at E14.5, apoptotic cells were found in the medial edge seam at anterior, middle and posterior region of the developing palate, particularly in the nasal and oral epithelial triangles in wild-type samples, but, no apoptotic positive cells were detected in the medial edge seam in the anterior, middle and posterior region of palate in mutant samples

• at E14.5, medial edge epithelial cells in the mutant palate still maintained the ability to proliferate throughout the entire palate, as measured by BrdU incorporation, and prevented palatal fusion in the middle and posterior part of the mutant palate sample, while there was no proliferation activity in the MEE of the wild-type sample

abnormal hard palate morphology ( J:112634 )

• a transversal section showed that the muscle attachments were misdirected anteriorly and attached onto the posterior portion of the bony palate, a typical malformation of the submucous cleft

abnormal soft palate morphology ( J:208431 )

• cell proliferation is reduced in the soft palate at E14.5 and E15.5, however apoptosis is unaffected

abnormal soft palate muscle morphology ( J:208431 )

• total volume of muscle in the soft palate is reduced at E15.5

small levator veli palatini muscle ( J:208431 )

• levator veli palatini muscle is reduced in volume and is smaller in newborns

small tensor veli palatini muscle ( J:208431 )

• tensor veli palatini is reduced in volume and is smaller in newborns

cleft secondary palate ( J:112634 )

• a complete cleft was manifested in the posterior part of the soft palate

cleft soft palate ( J:208431 )

• 100% of mice develop cleft soft palate, with cleft seen from E15.5 onwards

abnormal nasal septum morphology ( J:112634 )

• the nasal septum failed to fuse with the palatal shelves

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cleft soft palate		DOID:0110214	OMIM:119570	J:208431

Genotype
MGI:3761678

cn18

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(CD207-cre)1Dhka/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL/J

immune system

decreased Langerhans cell number ( J:126147 )

• although the number of Langerhans cells is substantially reduced compared to in wild-type mice, a variable number of Langerhans cells are present in the epidermis (0.02% to 0.59% of total epidermal cells compared to 0.46% to 0.89% in wild-type mice)

• the ratio of Langerhans cells in the epidermis increases with age

hematopoietic system

decreased Langerhans cell number ( J:126147 )

• although the number of Langerhans cells is substantially reduced compared to in wild-type mice, a variable number of Langerhans cells are present in the epidermis (0.02% to 0.59% of total epidermal cells compared to 0.46% to 0.89% in wild-type mice)

• the ratio of Langerhans cells in the epidermis increases with age

Genotype
MGI:5514247

cn19

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Foxp3-EGFP/cre)1cJbs/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * NOD * SJL

immune system

immune system phenotype ( J:196160 )

N • mice do not develop diabetes

N • normal T reg numbers in the spleen and pancreatic lymph nodes

increased regulatory T cell number ( J:196160 )

• in the thymus

hematopoietic system

increased regulatory T cell number ( J:196160 )

• in the thymus

Genotype
MGI:4398920

cn20

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Acvrl1-cre)L1Spo/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

normal phenotype

no abnormal phenotype detected ( J:130020 )

• mice are viable and exhibit normal vasculature

cardiovascular system

cardiovascular system phenotype ( J:130020 )

N • mice exhibit normal vasculature

Genotype
MGI:4943503

cn21

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:143910 )

• fetuses die by E16-E17 due to multi-organ abnormalities

respiratory system

abnormal branching involved in lung morphogenesis ( J:143910 )

• epithelial branching morphogenesis is disrupted causing cystic malformations in proximal airways

• however, lung epithelial cell identity and differentiation remain unaffected

abnormal lung lobe morphology ( J:143910 )

• at E15.5, both the shape and size of lung lobes is abnormal

• however, the overall process of lobation and number of lobes are normal

abnormal bronchus morphology ( J:143910 )

• abnormal epithelial morphogenesis results in cystic, dilated bronchi that lack parabronchial smooth muscle cells

abnormal bronchial cartilage morphology ( J:143910 )

• at E15.5, the first and the second generation bronchi are devoid of cartilage

dilated respiratory conducting tube ( J:143910 )

• at E15.5, fetuses display large, dilated proximal airways lined with columnar epithelial cells

abnormal tracheal cartilage morphology ( J:143910 )

• at E15.5, both the number and shape of tracheal cartilage is abnormal

decreased tracheal cartilage ring number ( J:143910 )

• at E15.5, the number of tracheal cartilage rings appears to be reduced

skeleton

abnormal tracheal cartilage morphology ( J:143910 )

• at E15.5, both the number and shape of tracheal cartilage is abnormal

decreased tracheal cartilage ring number ( J:143910 )

• at E15.5, the number of tracheal cartilage rings appears to be reduced