Phenotypes associated with this allele

• Allele Symbol: Tg(MtTGFA)42Lmb
• Allele Name: transgene insertion 42, Glenn Merlino
• Allele ID: MGI:2388567
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/0 Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3819967
cx2	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+ Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3820248
cx3	Tg(Alb1-Myc)#Sst/0 Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3820251
cx4	Nphp3^pcy/Nphp3^pcy Tg(MtTGFA)42Lmb/0	involves: CD-1 * DBA/2Fg * KK	MGI:3800129
tg5	Tg(MtTGFA)42Lmb/Tg(MtTGFA)42Lmb	involves: CD-1	MGI:3799643
tg6	Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CD-1	MGI:3799645
tg7	Tg(MtTGFA)42Lmb/0	involves: CD-1	MGI:3800166
tg8	Tg(MtTGFA)42Lmb/0	involves: CD-1 * FVB/N	MGI:3799646

Genotype
MGI:3819967

cx1

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/0; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

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

neoplasm

increased hepatocellular carcinoma incidence ( J:4527 )

• three weeks after zinc administration through drinking water, the first signs of hepatic neoplasia are evident with large hepatocytes with compact nuclei being found around blood vessels

• after six weeks of zinc administration, 80% of mice display these neoplastic lesions

• after ten weeks of zinc administration, foci of dysplastic cells are found throughout the liver nodule

• intravascular spread of tumor cells is also observed ten weeks after zinc administration

• after 16 weeks of zinc administration, over 70% of mice carry single or multifocal nodules of which one quarter consist of well differentiated hepatocellular carcinomas displaying pseudoglandular or trabecular pattern

• the appearance of preneoplastic and neoplastic lesions also occur in mice with a delay of 6 to 8 weeks in mice not receiving zinc treatment

liver/biliary system

increased hepatocellular carcinoma incidence ( J:4527 )

• three weeks after zinc administration through drinking water, the first signs of hepatic neoplasia are evident with large hepatocytes with compact nuclei being found around blood vessels

• after six weeks of zinc administration, 80% of mice display these neoplastic lesions

• after ten weeks of zinc administration, foci of dysplastic cells are found throughout the liver nodule

• intravascular spread of tumor cells is also observed ten weeks after zinc administration

• after 16 weeks of zinc administration, over 70% of mice carry single or multifocal nodules of which one quarter consist of well differentiated hepatocellular carcinomas displaying pseudoglandular or trabecular pattern

• the appearance of preneoplastic and neoplastic lesions also occur in mice with a delay of 6 to 8 weeks in mice not receiving zinc treatment

Genotype
MGI:3820248

cx2

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

liver/biliary system

increased hepatocyte apoptosis ( J:34434 )

• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

increased liver weight ( J:34434 )

• the liver weight/body weight ratio of young mice is significantly higher than controls

• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger

• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity

abnormal hepatocyte morphology ( J:34434 )

• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced polymorphisms with severe cytomegaly and karyomegaly

• hepatocytes often display abnormal nuclear structures (tripolar mitosis, chromosome bridges, aberrant chromosomal migration, intranuclear lipid droplets, and nuclear eosinophilic pseudoinclusions)

• these dysplastic changes started in the perivascular areas of the liver, are most advanced around the central veins and are spreading throughout the hepatic lobe

• metastasis to the lung and spleen is observed only rarely

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

multifocal hepatic necrosis ( J:34434 )

• focal coagulative necrosis of hepatocyte groups with granulocytic reaction is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

increased hepatocellular carcinoma incidence ( J:34434 )

• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age

• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)

• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable

• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis

• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

neoplasm

increased hepatocellular carcinoma incidence ( J:34434 )

• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age

• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)

• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable

• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis

• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

cellular

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

increased hepatocyte apoptosis ( J:34434 )

• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

growth/size/body

increased liver weight ( J:34434 )

• the liver weight/body weight ratio of young mice is significantly higher than controls

• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger

• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:34434

Genotype
MGI:3820251

cx3

• Allelic Composition: Tg(Alb1-Myc)#Sst/0; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

liver/biliary system

increased hepatocyte apoptosis ( J:34434 )

• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

increased liver weight ( J:34434 )

• the liver weight/body weight ratio of young mice is significantly higher than controls

• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger

• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity

abnormal hepatocyte morphology ( J:34434 )

• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced polymorphisms with severe cytomegaly and karyomegaly

• hepatocytes often display abnormal nuclear structures (tripolar mitosis, chromosome bridges, aberrant chromosomal migration, intranuclear lipid droplets, and nuclear eosinophilic pseudoinclusions)

• these dysplastic changes started in the perivascular areas of the liver, are most advanced around the central veins and are spreading throughout the hepatic lobe

• metastasis to the lung and spleen is observed only rarely

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

multifocal hepatic necrosis ( J:34434 )

• focal coagulative necrosis of hepatocyte groups with granulocytic reaction is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

increased hepatocellular carcinoma incidence ( J:34434 )

• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age

• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)

• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable

• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis

• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

neoplasm

increased hepatocellular carcinoma incidence ( J:34434 )

• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age

• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)

• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable

• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis

• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern

• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

cellular

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

increased hepatocyte apoptosis ( J:34434 )

• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

growth/size/body

increased liver weight ( J:34434 )

• the liver weight/body weight ratio of young mice is significantly higher than controls

• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger

• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity

Genotype
MGI:3800129

cx4

• Allelic Composition: Nphp3^pcy/Nphp3^pcy; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: CD-1 * DBA/2Fg * KK

renal/urinary system

polycystic kidney ( J:129264 )

• cysts are first observed in mice supplemented with zinc at 4 to 6.5 weeks and progresses

• at 8.5 weeks, cyst size is larger than in wild-type mice and Nphp3^pcy homozygotes

enlarged kidney ( J:129264 )

• at 8.5 weeks, kidney size is increased compared to in wild-type mice and Nphp3^pcy homozygotes

growth/size/body

polycystic kidney ( J:129264 )

• cysts are first observed in mice supplemented with zinc at 4 to 6.5 weeks and progresses

• at 8.5 weeks, cyst size is larger than in wild-type mice and Nphp3^pcy homozygotes

enlarged kidney ( J:129264 )

• at 8.5 weeks, kidney size is increased compared to in wild-type mice and Nphp3^pcy homozygotes

Genotype
MGI:3799643

tg5

• Allelic Composition: Tg(MtTGFA)42Lmb/Tg(MtTGFA)42Lmb
• Genetic Background: involves: CD-1

cellular

increased hepatocyte karyomegaly ( J:28452 )

• after 2 months of age

increased mesangial cell number ( J:20315 )

• in mice supplemented with zinc

endocrine/exocrine glands

abnormal mammary gland development ( J:28452 )

♀ • at 6 weeks of age, zinc treated females exhibit a delay in epithelium penetration into the mesenchymal fat pad compared to wild-type mice

♀ • at 7 weeks of age, active epithelial cells are located in the subtending duct as well as the end bud region compared to wild-type mice in which active cells are only located in the end bud region

♀ • however, by week 12 mammary development is normal

abnormal pancreas morphology ( J:28452 )

• the pancreas shows progressive hyperplasia of the stroma, tubular structures, and florid ductular metaplasia

pancreas fibrosis ( J:28452 )

• exposure to zinc increases severity of lesions

• older mice exhibit severe perilobular and intralobular fibrosis

• pancreatic fibrosis is less severe in zinc restricted mice

liver/biliary system

abnormal liver morphology ( J:28452 )

• mice exhibit progressive liver lesions that begin after 2 months of age with karyomegaly and cytomegaly of hepatocytes

• at 7 to 8 months of age, mice exhibit foci's heterogeneity of cell size and cellular dysplasia in the liver

• mice exhibit single to multiple foci liver nodules of 0.5 cm in diameter or greater

• liver lesions develop in a progressive fashion, with neoplasia confirmed at autopsy

enlarged liver ( J:28452 )

• in severe cases mice exhibit enlarged livers due to the presence of nodular masses

abnormal hepatocyte morphology ( J:28452 )

• after 2 months of age, mice exhibit foci of hepatocytes that exhibit karyomegaly and cytomegaly

increased hepatocyte karyomegaly ( J:28452 )

• after 2 months of age

increased hepatocellular carcinoma incidence ( J:28452 )

• mice exhibit heptatocellular carcinomas that are none metastatic

• exposure to zinc increases severity of lesions

renal/urinary system

kidney cyst ( J:20315 )

• occasionally cysts are of proximal tubular origins

• female mice supplemented with zinc exhibit renal cysts of distal tubule origins unlike in similarly treated wild-type mice

• renal cysts in female mice supplemented with zinc are frequently associated with fibrosis

• some male mice supplemented with zinc exhibit renal cysts

increased kidney weight ( J:20315 )

• in female mice supplemented with zinc compared to similarly treated wild-type mice

abnormal glomerular mesangium morphology ( J:20315 )

• mice supplemented with zinc exhibit increased mesangial compartments due to increased mesangial cell numbers and space compared to similarly treated wild-type mice

increased mesangial cell number ( J:20315 )

• in mice supplemented with zinc

expanded mesangial matrix ( J:20315 )

• in mice supplemented with zinc

renal glomerulus hypertrophy ( J:20315 )

• mice supplemented with zinc exhibit enlarged glomeruli compared to similarly treated wild-type mice

renal fibrosis ( J:20315 )

• renal cysts in female mice supplemented with zinc are frequently associated with fibrosis

neoplasm

increased hepatocellular carcinoma incidence ( J:28452 )

• mice exhibit heptatocellular carcinomas that are none metastatic

• exposure to zinc increases severity of lesions

growth/size/body

increased body weight ( J:20315 )

• in mice supplemented with zinc compared to similarly treated wild-type mice

kidney cyst ( J:20315 )

• female mice supplemented with zinc exhibit renal cysts of distal tubule origins unlike in similarly treated wild-type mice

• renal cysts in female mice supplemented with zinc are frequently associated with fibrosis

• occasionally cysts are of proximal tubular origins

• some male mice supplemented with zinc exhibit renal cysts

increased kidney weight ( J:20315 )

• in female mice supplemented with zinc compared to similarly treated wild-type mice

enlarged liver ( J:28452 )

• in severe cases mice exhibit enlarged livers due to the presence of nodular masses

immune system

immune system phenotype ( J:28452 )

N • mice are not diabetic and have no obvious inflammatory reaction

integument

abnormal mammary gland development ( J:28452 )

♀ • at 6 weeks of age, zinc treated females exhibit a delay in epithelium penetration into the mesenchymal fat pad compared to wild-type mice

♀ • at 7 weeks of age, active epithelial cells are located in the subtending duct as well as the end bud region compared to wild-type mice in which active cells are only located in the end bud region

♀ • however, by week 12 mammary development is normal

Genotype
MGI:3799645

tg6

• Allelic Composition: Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CD-1

neoplasm

increased liver tumor incidence ( J:2578 )

• mice develop liver tumors at the same frequency as on a CD-1 background

liver/biliary system

increased liver tumor incidence ( J:2578 )

• mice develop liver tumors at the same frequency as on a CD-1 background

Genotype
MGI:3800166

tg7

• Allelic Composition: Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: CD-1

homeostasis/metabolism

increased noradrenaline level ( J:127695 )

• noradrenaline levels in the hypothalamus are elevated in female mice compared to wild-type mice

increased serotonin level ( J:127695 )

• serotonine levels in the cortex and brain are elevated in female mice compared to wild-type mice

• the ratio of 5-HIAA and 5-HT (indicating serotonine turn over) is reduced in the male brain stem and the female frontal cortex compared to in wild-type mice

Genotype
MGI:3799646

tg8

• Allelic Composition: Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: CD-1 * FVB/N

neoplasm

increased liver tumor incidence ( J:2578 )

• Background Sensitivity: mice develop fewer liver tumors than on a CD-1 or C57BL/6 and CD-1 background

liver/biliary system

increased liver tumor incidence ( J:2578 )

• Background Sensitivity: mice develop fewer liver tumors than on a CD-1 or C57BL/6 and CD-1 background