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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain FVB Donor Strain 129S6 via TC1 ES cell line   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice homozygous for the targeted mutation are viable, develop normally, and are fertile, but do not lactate. Mammary ductal development through pregnancy is normal, but lobuloalveolar development is severely reduced and there is no milk secretion even after prolonged suckling. Levels of the closely related STAT5B signalling molecule are also markedly reduced in STAT5A-deficient mice, but levels increase and phosphorylation is evident after 3 days of suckling. Expression of several milk protein genes is unaffected in homozygous mutants, whereas whey acidic protein expression is severely reduced. Homozygous males exhibit abnormal prostate morphology and an increase in probasin secretion. Immmunological defects exhibited by homozygotes include a reduced number of peritoneal mast cells, decreased IL-3 dependent development of bone marrow-derived mast cells, defective bone marrow-derived macrophage GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) induced proliferation, decreased number of NK cells and decreased expansion of T cells. This mutant mouse strain may be useful in studies of mammary gland development, lactogenesis, hematopoiesis, and immunological intracellular signal transduction.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing phosphoglycerate kinase promoter driven neomycin resistance gene and a herpes simplex virus thymidine kinase gene was used to disrupt a region containing a non-coding exon, 2 coding exons and flanking sequence. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to 129 mice, and then backcrossed to FVB for 6 generations.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Stat5a^tm1Mam allele

002833	B6;129S6-Stat5atm1Mam/J
007806	C.129S(B6)-Stat5atm1Mam/J

View Strains carrying   Stat5a^tm1Mam     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Stat5a^tm1Mam/Stat5a^tm1Mam

        either: 129S6/SvEvTac-Stat5a^tm1Mam or (involves: 129S6/SvEvTac * NIH Black Swiss)

• endocrine/exocrine gland phenotype
• abnormal mammary gland development   (MGI Ref ID J:64278)
• • abnormal branching of the mammary ductal tree
    • ductal development appears normal but lobuloalveolar outgrowth is severely reduced, secretory tissue is sparse, and alveoli are petite and contain small lumina   (MGI Ref ID J:64278)
  • abnormal mammary gland growth during lactation
    • lubuloalveolar units are underdeveloped and do not exhibit a secretory phenotype, even after maximal stimulation of prolactin secretion induced by suckling   (MGI Ref ID J:64278)
  • abnormal mammary gland growth during pregnancy
    • mammary lobuloalveolar outgrowth during pregnancy is curtailed   (MGI Ref ID J:64278)
• lactation failure
  • females fail to lactate after parturition because of a failure of terminal differentiation   (MGI Ref ID J:64278)
  • continued suckling does not result in milk production and release, however expression of milk protein genes and synthesis of milk proteins is maintained and the gland does not involute   (MGI Ref ID J:64278)
• reproductive system phenotype
• abnormal mammary gland growth during pregnancy
  • mammary lobuloalveolar outgrowth during pregnancy is curtailed   (MGI Ref ID J:64278)
• integument phenotype
• abnormal mammary gland development   (MGI Ref ID J:64278)
• • abnormal branching of the mammary ductal tree
    • ductal development appears normal but lobuloalveolar outgrowth is severely reduced, secretory tissue is sparse, and alveoli are petite and contain small lumina   (MGI Ref ID J:64278)
  • abnormal mammary gland growth during lactation
    • lubuloalveolar units are underdeveloped and do not exhibit a secretory phenotype, even after maximal stimulation of prolactin secretion induced by suckling   (MGI Ref ID J:64278)
  • abnormal mammary gland growth during pregnancy
    • mammary lobuloalveolar outgrowth during pregnancy is curtailed   (MGI Ref ID J:64278)
• lactation failure
  • females fail to lactate after parturition because of a failure of terminal differentiation   (MGI Ref ID J:64278)
  • continued suckling does not result in milk production and release, however expression of milk protein genes and synthesis of milk proteins is maintained and the gland does not involute   (MGI Ref ID J:64278)

Stat5a^tm1Mam/Stat5a^tm1Mam

        involves: 129S6/SvEvTac

• endocrine/exocrine gland phenotype
• abnormal prostate gland epithelium morphology
  • prostate is characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates   (MGI Ref ID J:63495)
  • affected acini are filled with desquamated, granular epithelial cells that become embedded in dense, coagulated secretory material, resulting in glandular cyst formation   (MGI Ref ID J:63495)
• abnormal prostate gland physiology
  • exhibit an increase in prostate secretion of probasin   (MGI Ref ID J:63495)
• prostate gland cysts
  • on average, 10.6% show cystic prostates compared to 1% in wild-type, however do not show changes in prostate size or epithelial hyperplasia   (MGI Ref ID J:63495)
• reproductive system phenotype
• abnormal prostate gland epithelium morphology
  • prostate is characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates   (MGI Ref ID J:63495)
  • affected acini are filled with desquamated, granular epithelial cells that become embedded in dense, coagulated secretory material, resulting in glandular cyst formation   (MGI Ref ID J:63495)
• abnormal prostate gland physiology
  • exhibit an increase in prostate secretion of probasin   (MGI Ref ID J:63495)
• prostate gland cysts
  • on average, 10.6% show cystic prostates compared to 1% in wild-type, however do not show changes in prostate size or epithelial hyperplasia   (MGI Ref ID J:63495)

Stat5a^tm1Mam/Stat5a^tm1Mam

        C.129S6-Stat5a^tm1Mam

• immune system phenotype
• abnormal mast cell morphology
  • IL-3-induced but not stem cell factor-induced proliferation of bone marrow derived mast cells is significantly diminished   (MGI Ref ID J:101855)
  • survival rates of both peritoneal mast cells and bone marrow derived mast cells are decreased and apoptotic cells are increased   (MGI Ref ID J:101855)
• • abnormal mast cell differentiation
    • the IL-3-dependent development of bone marrow derived mast cells is decreased   (MGI Ref ID J:101855)
  • decreased mast cell number
    • decrease in the number of mast cells in the peritoneal cavity, ear and stomach   (MGI Ref ID J:101855)
• hematopoietic system phenotype
• abnormal mast cell morphology
  • IL-3-induced but not stem cell factor-induced proliferation of bone marrow derived mast cells is significantly diminished   (MGI Ref ID J:101855)
  • survival rates of both peritoneal mast cells and bone marrow derived mast cells are decreased and apoptotic cells are increased   (MGI Ref ID J:101855)
• • abnormal mast cell differentiation
    • the IL-3-dependent development of bone marrow derived mast cells is decreased   (MGI Ref ID J:101855)
  • decreased mast cell number
    • decrease in the number of mast cells in the peritoneal cavity, ear and stomach   (MGI Ref ID J:101855)
• cellular phenotype
• abnormal mast cell differentiation
  • the IL-3-dependent development of bone marrow derived mast cells is decreased   (MGI Ref ID J:101855)

Stat5a^tm1Mam/Stat5a^tm1Mam

        involves: 129S6/SvEvTac * C57BL/6

• immune system phenotype
• decreased NK cell number
  • the percentage of NK cells is diminished (about 70% of the percentage seen in wild-type) although to a lesser extent than in Stat5b^tm1Hwd homozygotes   (MGI Ref ID J:112035)
• decreased splenocyte number
  • exhibit decreased numbers of splenocytes   (MGI Ref ID J:112035)
• impaired natural killer cell mediated cytotoxicity
  • NK cytolytic activity is impaired but to a lesser extent than seen in Stat5b^tm1Hwd homozygotes   (MGI Ref ID J:112035)
• hematopoietic system phenotype
• decreased NK cell number
  • the percentage of NK cells is diminished (about 70% of the percentage seen in wild-type) although to a lesser extent than in Stat5b^tm1Hwd homozygotes   (MGI Ref ID J:112035)
• decreased splenocyte number
  • exhibit decreased numbers of splenocytes   (MGI Ref ID J:112035)

View Research Applications

Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Stat5a^tm1Mam related

Cancer Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Mast Cell Deficiency
Intracellular Signaling Molecules

Research Tools
Immunology and Inflammation Research
      Mast Cell Deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Stat5atm1Mam
Allele Name		targeted mutation 1, Lothar Hennighausen
Allele Type		Targeted (knock-out)
Common Name(s)		Stat5a-;
Mutation Made By		Dr. Lothar Hennighausen,   National Institutes of Health
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC1/TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Stat5a, signal transducer and activator of transcription 5A
Chromosome		11
Gene Common Name(s)		AA959963; MGF; STAT5; expressed sequence AA959963;
Molecular Note		The promoter sequence, an untranslated exon, and two coding exons were replaced by a neomycin selection cassette. Western blot analysis of extracts immunoprecipitated from mammary tissue of homozygous mutant mice showed an absence of encoded protein. [MGI Ref ID J:64278]

Genotyping

Genotyping Information

Genotyping Protocols

Stat5a^tm1Mam, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liu X; Robinson GW; Wagner KU; Garrett L; Wynshaw-Boris A; Hennighausen L. 1997. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11(2):179-86. [PubMed: 9009201]  [MGI Ref ID J:64278]

Additional References

Stat5a^tm1Mam related

Cain JA; Xiang Z; O'Neal J; Kreisel F; Colson A; Luo H; Hennighausen L; Tomasson MH. 2007. Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage. Blood 109(9):3906-14. [PubMed: 17218386]  [MGI Ref ID J:145325]

Clodfelter KH; Miles GD; Wauthier V; Holloway MG; Zhang X; Hodor P; Ray WJ; Waxman DJ. 2007. Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysis. Physiol Genomics 31(1):63-74. [PubMed: 17536022]  [MGI Ref ID J:127170]

Feldman GM; Rosenthal LA; Liu X; Hayes MP; Wynshaw-Boris A; Leonard WJ; Hennighausen L; Finbloom DS. 1997. STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression. Blood 90(5):1768-76. [PubMed: 9292509]  [MGI Ref ID J:43349]

Ikeda K; Nakajima H; Suzuki K; Watanabe N; Kagami S; Iwamoto I. 2005. Stat5a is essential for the proliferation and survival of murine mast cells. Int Arch Allergy Immunol 137 Suppl 1:45-50. [PubMed: 15947484]  [MGI Ref ID J:101855]

Imada K; Bloom ET; Nakajima H; Horvath-Arcidiacono JA; Udy GB; Davey HW; Leonard WJ. 1998. Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity. J Exp Med 188(11):2067-74. [PubMed: 9841920]  [MGI Ref ID J:112035]

Kagami S; Nakajima H; Kumano K; Suzuki K; Suto A; Imada K; Davey HW; Saito Y; Takatsu K; Leonard WJ; Iwamoto I. 2000. Both stat5a and stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue. Blood 95(4):1370-7. [PubMed: 10666213]  [MGI Ref ID J:106678]

Kagami S; Nakajima H; Suto A; Hirose K; Suzuki K; Morita S; Kato I; Saito Y; Kitamura T; Iwamoto I. 2001. Stat5a regulates T helper cell differentiation by several distinct mechanisms. Blood 97(8):2358-65. [PubMed: 11290598]  [MGI Ref ID J:68803]

Kelly J; Spolski R; Imada K; Bollenbacher J; Lee S; Leonard WJ. 2003. A role for stat5 in CD8(+) T cell homeostasis. J Immunol 170(1):210-7. [PubMed: 12496402]  [MGI Ref ID J:80897]

Kelly JA; Spolski R; Kovanen PE; Suzuki T; Bollenbacher J; Pise-Masison CA; Radonovich MF; Lee S; Jenkins NA; Copeland NG; Morse HC 3rd; Leonard WJ. 2003. Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma. J Exp Med 198(1):79-89. [PubMed: 12835478]  [MGI Ref ID J:84460]

Kovanen PE; Young L; Al-Shami A; Rovella V; Pise-Masison CA; Radonovich MF; Powell J; Fu J; Brady JN; Munson PJ; Leonard WJ. 2005. Global analysis of IL-2 target genes: identification of chromosomal clusters of expressed genes. Int Immunol 17(8):1009-21. [PubMed: 15980098]  [MGI Ref ID J:104228]

Le Provost F; Miyoshi K; Vilotte JL; Bierie B; Robinson GW; Hennighausen L. 2005. SOCS3 promotes apoptosis of mammary differentiated cells. Biochem Biophys Res Commun 338(4):1696-701. [PubMed: 16289036]  [MGI Ref ID J:104012]

Liu X; Gallego MI; Smith GH; Robinson GW; Hennighausen L. 1998. Functional rescue of Stat5a-null mammary tissue through the activation of compensating signals including Stat5b. Cell Growth Differ 9(9):795-803. [PubMed: 9751123]  [MGI Ref ID J:112998]

Liu YE; Pu W; Wang J; Kang JX; Shi YE. 2007. Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids. FEBS J 274(13):3351-62. [PubMed: 17547694]  [MGI Ref ID J:125734]

Miermont AM; Parrish AR; Furth PA. 2010. Role of ERalpha in the differential response of Stat5a loss in susceptibility to mammary preneoplasia and DMBA-induced carcinogenesis. Carcinogenesis 31(6):1124-31. [PubMed: 20181624]  [MGI Ref ID J:160715]

Nakajima H; Liu XW; Wynshaw-Boris A; Rosenthal LA; Imada K; Finbloom DS; Hennighausen L; Leonard WJ. 1997. An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. Immunity 7(5):691-701. [PubMed: 9390692]  [MGI Ref ID J:111527]

Nevalainen MT; Ahonen TJ; Yamashita H; Chandrashekar V; Bartke A; Grimley PM; Robinson GW; Hennighausen L; Rui H. 2000. Epithelial defect in prostates of Stat5a-null mice. Lab Invest 80(7):993-1006. [PubMed: 10908145]  [MGI Ref ID J:63495]

Park SH; Liu X; Hennighausen L; Davey HW; Waxman DJ. 1999. Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene expression. Impact of STAT5a gene disruption. J Biol Chem 274(11):7421-30. [PubMed: 10066807]  [MGI Ref ID J:53864]

Porpiglia E; Hidalgo D; Koulnis M; Tzafriri AR; Socolovsky M. 2012. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities. PLoS Biol 10(8):e1001383. [PubMed: 22969412]  [MGI Ref ID J:191770]

Reichenstein M; Rauner G; Barash I. 2011. Conditional repression of STAT5 expression during lactation reveals its exclusive roles in mammary gland morphology, milk-protein gene expression, and neonate growth. Mol Reprod Dev 78(8):585-96. [PubMed: 21688337]  [MGI Ref ID J:175636]

Takatori H; Nakajima H; Hirose K; Kagami S; Tamachi T; Suto A; Suzuki K; Saito Y; Iwamoto I. 2005. Indispensable role of Stat5a in Stat6-independent Th2 cell differentiation and allergic airway inflammation. J Immunol 174(6):3734-40. [PubMed: 15749913]  [MGI Ref ID J:97701]

Takatori H; Nakajima H; Kagami S; Hirose K; Suto A; Suzuki K; Kubo M; Yoshimura A; Saito Y; Iwamoto I. 2005. Stat5a inhibits IL-12-induced Th1 cell differentiation through the induction of suppressor of cytokine signaling 3 expression. J Immunol 174(7):4105-12. [PubMed: 15778369]  [MGI Ref ID J:97961]

Tsukamoto Y; Uehara S; Mizoguchi C; Sato A; Horikawa K; Takatsu K. 2005. Requirement of 8-mercaptoguanosine as a costimulus for IL-4-dependent mu to gamma1 class switch recombination in CD38-activated B cells. Biochem Biophys Res Commun 336(2):625-33. [PubMed: 16143305]  [MGI Ref ID J:101014]

Wan CK; Oh J; Li P; West EE; Wong EA; Andraski AB; Spolski R; Yu ZX; He J; Kelsall BL; Leonard WJ. 2013. The Cytokines IL-21 and GM-CSF Have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells. Immunity 38(3):514-27. [PubMed: 23453633]  [MGI Ref ID J:194831]

Yagi J; Arimura Y; Takatori H; Nakajima H; Iwamoto I; Uchiyama T. 2006. Genetic background influences Th cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4+ T cells. Int Immunol 18(12):1681-90. [PubMed: 17035345]  [MGI Ref ID J:116067]

Ye D; Wolff N; Li L; Zhang S; Ilaria RL Jr. 2006. STAT5 signaling is required for the efficient induction and maintenance of CML in mice. Blood 107(12):4917-25. [PubMed: 16522816]  [MGI Ref ID J:133001]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred heterozygous females X homozygous males. Although homozygous females are viable and fertile, they do not lactate. Litters from homozygous females must be fostered.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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