Strain Name:

STOCK Tg(MtTGFA)42Lmb/J

Stock Number:

002422

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+N2
 
Donating Investigator Glenn Merlino,   National Institutes of Health

Description
In the STOCK Tg(MtTGFA)42Lmb/J line liver lesions develop in a progressive fashion, with neoplasia confirmed at autopsy (average age 13 months). Pancreas showed progressive hyperplasia of the stroma, tubular structures and ductular metaplasia, with penetrance of 100%. Unlike mice from the FVB/N-Tg(MtTGFA)100Lmb/J line, STOCK Tg(MtTGFA)42Lmb/J mice do not develop mammary tumors.

Related Strains

Strains carrying   Tg(MtTGFA)42Lmb allele
003722   SW.Cg-Tg(MtTGFA)42Lmb/J
View Strains carrying   Tg(MtTGFA)42Lmb     (1 strain)

View Strains carrying other alleles of Mt1     (12 strains)

Strains carrying other alleles of TGFA
002459   B6D2-Tg(MMTVTGFA)254Rjc/J
002373   B6D2-Tg(MMTVTGFA)29Rjc/J
002953   FVB.Cg-Tg(MMTVTGFA)254Rjc/J
002421   FVB/N-Tg(MtTGFA)100Lmb/J
View Strains carrying other alleles of TGFA     (4 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(MtTGFA)42Lmb/0

        involves: C57BL/6 * CD-1
  • tumorigenesis
  • liver tumor (MGI Ref ID J:2578)
    • mice develop liver tumors at the same frequency as on a CD-1 background

Tg(MtTGFA)42Lmb/0

        involves: CD-1 * FVB/N
  • tumorigenesis
  • liver tumor (MGI Ref ID J:2578)
    • mice develop fewer liver tumors than on a CD-1 or C57BL/6 and CD-1 background

Tg(MtTGFA)42Lmb/0

        involves: CD-1
  • homeostasis/metabolism phenotype
  • abnormal noradrenaline level (MGI Ref ID J:127695)
    • noradrenaline levels in the hypothalamus are elevated in female mice compared to wild-type mice
  • abnormal serotonin level (MGI Ref ID 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

Tg(MtTGFA)42Lmb/Tg(MtTGFA)42Lmb

        involves: CD-1
  • endocrine/exocrine gland phenotype
  • abnormal mammary gland development (MGI Ref ID 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 (MGI Ref ID J:28452)
    • the pancreas shows progressive hyperplasia of the stroma, tubular structures, and florid ductular metaplasia
    • pancreas fibrosis (MGI Ref ID 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 phenotype
  • abnormal liver morphology (MGI Ref ID 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
    • abnormal hepatocyte morphology (MGI Ref ID J:28452)
      • after 2 months, mice exhibit foci of hepatocytes that exhibit karyomegaly and cytomegaly
    • enlarged liver (MGI Ref ID J:28452)
      • in severe cases mice exhibit enlarged livers due to the presence of nodular masses
  • renal/urinary system phenotype
  • abnormal renal glomerulus morphology (MGI Ref ID J:20315)
    • mice supplemented with zinc exhibit enlarged glomeruli and increased mesangial compartments due to increased mesangial cells and space compared to similarly treated wild-type mice
    • abnormal mesangial cell (MGI Ref ID J:20315)
      • mice supplemented with zinc exhibit increased mesangial compartments due to increased mesangial cells and space compared to similarly treated wild-type mice
  • increased kidney weight (MGI Ref ID J:20315)
    • in female mice supplemented with zinc compared to similarly treated wild-type mice
  • kidney cysts (MGI Ref ID 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
  • renal fibrosis (MGI Ref ID J:20315)
    • renal cysts in female mice supplemented with zinc are frequently associated with fibrosis
  • tumorigenesis
  • hepatocellular carcinoma (MGI Ref ID J:28452)
    • mice exhibit heptatocellular carcinomas that are none metastatic
    • exposure to zinc increases severity of lesions
  • growth/size phenotype
  • increased body weight (MGI Ref ID J:20315)
    • in mice supplemented with zinc compared to similarly treated wild-type mice
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:28452)
    • mice are not diabetic and have no obvious inflammatory reaction
  • reproductive system phenotype
  • abnormal mammary gland development (MGI Ref ID 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
  • digestive/alimentary phenotype
  • abnormal pancreas morphology (MGI Ref ID J:28452)
    • the pancreas shows progressive hyperplasia of the stroma, tubular structures, and florid ductular metaplasia
    • pancreas fibrosis (MGI Ref ID 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
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence (Other Tissues/Organs)

Mt1 related

Metabolism Research

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(MtTGFA)42Lmb
Allele Name transgene insertion 42, Glenn Merlino
Allele Type Transgenic (random, expressed)
Common Name(s) MT-TGF-alpha; MT/TGF-alpha line MT42; MT42; TGF-alpha; Tg(Mt1-TGFA)42Lmb; line MT42;
Mutation Made By Glenn Merlino,   National Institutes of Health
Strain of OriginCD-1
Expressed Gene TGFA, transforming growth factor, alpha, human
Promoter Mt1, metallothionein 1, mouse, laboratory
Molecular Note This transgene contains the inducible mouse Mt1 (metallothionein) promoter, cDNA of the wild-type allele of the human TGFA (transforming growth factor alpha) gene, and a human growth hormone polyadenylation signal. Line 100, carrying 10 copies of the transgene was also produced (see Tg(MtTGFA)100Lmb). [MGI Ref ID J:28452]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MtTGFA), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Jhappan C; Stahle C; Harkins RN; Fausto N; Smith GH; Merlino GT. 1990. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61(6):1137-46. [PubMed: 2350785]  [MGI Ref ID J:28452]

Additional References

Tg(MtTGFA)42Lmb related

Bockman DE; Merlino G. 1992. Cytological changes in the pancreas of transgenic mice overexpressing transforming growth factor alpha. Gastroenterology 103(6):1883-92. [PubMed: 1451981]  [MGI Ref ID J:80653]

Booth BW; Jhappan C; Merlino G; Smith GH. 2007. TGFbeta1 and TGFalpha contrarily affect alveolar survival and tumorigenesis in mouse mammary epithelium. Int J Cancer 120(3):493-9. [PubMed: 17096338]  [MGI Ref ID J:117812]

Calvisi DF; Factor VM; Ladu S; Conner EA; Thorgeirsson SS. 2004. Disruption of beta-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice. Gastroenterology 126(5):1374-86. [PubMed: 15131798]  [MGI Ref ID J:90164]

Calvisi DF; Factor VM; Loi R; Thorgeirsson SS. 2001. Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade. Cancer Res 61(5):2085-91. [PubMed: 11280770]  [MGI Ref ID J:68485]

Calvisi DF; Ladu S; Conner EA; Factor VM; Thorgeirsson SS. 2004. Disregulation of E-cadherin in transgenic mouse models of liver cancer. Lab Invest 84(9):1137-47. [PubMed: 15220935]  [MGI Ref ID J:91632]

Calvisi DF; Thorgeirsson SS. 2005. Molecular mechanisms of hepatocarcinogenesis in transgenic mouse models of liver cancer. Toxicol Pathol 33(1):181-4. [PubMed: 15805070]  [MGI Ref ID J:98665]

Durkin ME; Keck-Waggoner CL; Popescu NC; Thorgeirsson SS. 2001. Integration of a c-myc Transgene Results in Disruption of the Mouse Gtf2ird1 Gene, the Homologue of the Human GTF2IRD1 Gene Hemizygously Deleted in Williams-Beuren Syndrome. Genomics 73(1):20-7. [PubMed: 11352562]  [MGI Ref ID J:68983]

Gattone VH nd; Kuenstler KA; Lindemann GW; Lu X; Cowley BD Jr; Rankin CA; Calvet JP. 1996. Renal expression of a transforming growth factor-alpha transgene accelerates the progression of inherited, slowly progressive polycystic kidney disease in the mouse. J Lab Clin Med 127(2):214-22. [PubMed: 8636651]  [MGI Ref ID J:129264]

Hilakivi-Clarke LA; Corduban TD; Taira T; Hitri A; Deutsch S; Korpi ER; Goldberg R; Kellar KJ. 1995. Alterations in brain monoamines and GABAA receptors in transgenic mice overexpressing TGF alpha. Pharmacol Biochem Behav 50(4):593-600. [PubMed: 7617706]  [MGI Ref ID J:127695]

Hironaka K; Factor VM; Calvisi DF; Conner EA; Thorgeirsson SS. 2003. Dysregulation of DNA Repair Pathways in a Transforming Growth Factor alpha/c-myc Transgenic Mouse Model of Accelerated Hepatocarcinogenesis. Lab Invest 83(5):643-54. [PubMed: 12746474]  [MGI Ref ID J:83492]

Jhappan C; Takayama H; Dickson RB; Merlino G. 1994. Transgenic mice provide genetic evidence that transforming growth factor alpha promotes skin tumorigenesis via H-ras-dependent and H-ras-independent pathways. Cell Growth Differ 5(4):385-94. [PubMed: 8043512]  [MGI Ref ID J:81426]

Kakizaki S; Takagi H; Fukusato T; Toyoda M; Horiguchi N; Sato K; Takayama H; Nagamine T; Mori M. 2001. Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine. Int J Vitam Nutr Res 71(5):261-7. [PubMed: 11725690]  [MGI Ref ID J:72993]

Lowden DA; Lindemann GW; Merlino G; Barash BD; Calvet JP; Gattone VH 2nd. 1994. Renal cysts in transgenic mice expressing transforming growth factor-alpha [see comments] J Lab Clin Med 124(3):386-94. [PubMed: 8083581]  [MGI Ref ID J:20315]

Matsumoto T; Takagi H; Mori M. 2000. Androgen dependency of hepatocarcinogenesis in TGFalpha transgenic mice Liver 20(3):228-33. [PubMed: 10902973]  [MGI Ref ID J:63573]

Murakami H; Sanderson ND; Nagy P; Marino PA; Merlino G; Thorgeirsson SS. 1993. Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis. Cancer Res 53(8):1719-23. [PubMed: 8467484]  [MGI Ref ID J:4527]

Novoselov SV; Calvisi DF; Labunskyy VM; Factor VM; Carlson BA; Fomenko DE; Moustafa ME; Hatfield DL; Gladyshev VN. 2005. Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice. Oncogene 24(54):8003-11. [PubMed: 16170372]  [MGI Ref ID J:104079]

Puatanachokchai R; Kakuni M; Wanibuchi H; Kinoshita A; Kang JS; Salim EI; Morimura K; Tamano S; Merlino GT; Fukushima S. 2006. Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice. Asian Pac J Cancer Prev 7(2):274-8. [PubMed: 16839222]  [MGI Ref ID J:115804]

Santoni-Rugiu E; Jensen MR; Factor VM; Thorgeirsson SS. 1999. Acceleration of c-myc-induced hepatocarcinogenesis by Co-expression of transforming growth factor (TGF)-alpha in transgenic mice is associated with TGF-beta1 signaling disruption. Am J Pathol 154(6):1693-700. [PubMed: 10362794]  [MGI Ref ID J:55747]

Santoni-Rugiu E; Jensen MR; Thorgeirsson SS. 1998. Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor alpha. Cancer Res 58(1):123-34. [PubMed: 9426068]  [MGI Ref ID J:45016]

Santoni-Rugiu E; Nagy P; Jensen MR; Factor VM; Thorgeirsson SS. 1996. Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. Am J Pathol 149(2):407-28. [PubMed: 8701981]  [MGI Ref ID J:34434]

Sargent LM; Zhou X; Keck CL; Sanderson ND; Zimonjic DB; Popescu NC; Thorgeirsson SS. 1999. Nonrandom cytogenetic alterations in hepatocellular carcinoma from transgenic mice overexpressing c-Myc and transforming growth factor-alpha in the liver. Am J Pathol 154(4):1047-55. [PubMed: 10233843]  [MGI Ref ID J:79839]

Takagi H; Aida K; Sohara N; Mori M; Merlino G; Negishi M. 1997. Steroid hormone-dependent overexpression of cytochromes P450 2A in liver tumors of TGF alpha transgenic male mice. J Gastroenterol 32(5):708-11. [PubMed: 9350003]  [MGI Ref ID J:44697]

Takagi H; Sharp R; Hammermeister C; Goodrow T; Bradley MO; Fausto N; Merlino G. 1992. Molecular and genetic analysis of liver oncogenesis in transforming growth factor alpha transgenic mice. Cancer Res 52(19):5171-7. [PubMed: 1394122]  [MGI Ref ID J:2578]

Tamano S; Merlino GT; Ward JM. 1994. Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. Carcinogenesis 15(9):1791-8. [PubMed: 7923571]  [MGI Ref ID J:20676]

Vail ME; Pierce RH; Fausto N. 2001. Bcl-2 delays and alters hepatic carcinogenesis induced by transforming growth factor alpha. Cancer Res 61(2):594-601. [PubMed: 11212255]  [MGI Ref ID J:67450]

Wang TC; Bonner-Weir S; Oates PS; Chulak M; Simon B; Merlino GT; Schmidt EV; Brand SJ. 1993. Pancreatic gastrin stimulates islet differentiation of transforming growth factor alpha-induced ductular precursor cells. J Clin Invest 92(3):1349-56. [PubMed: 8376589]  [MGI Ref ID J:78615]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

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