Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. 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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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 lactation (MGI Ref ID J:64278)
  • females fail to lactate after parturition because of a failure of terminal differentiation
  • 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
• abnormal mammary gland development (MGI Ref ID J:64278)
• abnormal branching of the mammary ductal tree (MGI Ref ID J:64278)
  • ductal development appears normal but lobuloalveolar outgrowth is severely reduced, secretory tissue is sparse, and alveoli are petite and contain small lumina
• abnormal mammary gland growth during lactation (MGI Ref ID J:64278)
  • lubuloalveolar units are underdeveloped and do not exhibit a secretory phenotype, even after maximal stimulation of prolactin secretion induced by suckling
• abnormal mammary gland growth during pregnancy (MGI Ref ID J:64278)
  • mammary lobuloalveolar outgrowth during pregnancy is curtailed
• reproductive system phenotype
• abnormal lactation (MGI Ref ID J:64278)
  • females fail to lactate after parturition because of a failure of terminal differentiation
  • 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
• abnormal mammary gland development (MGI Ref ID J:64278)
• abnormal branching of the mammary ductal tree (MGI Ref ID J:64278)
  • ductal development appears normal but lobuloalveolar outgrowth is severely reduced, secretory tissue is sparse, and alveoli are petite and contain small lumina
• abnormal mammary gland growth during lactation (MGI Ref ID J:64278)
  • lubuloalveolar units are underdeveloped and do not exhibit a secretory phenotype, even after maximal stimulation of prolactin secretion induced by suckling
• abnormal mammary gland growth during pregnancy (MGI Ref ID J:64278)
  • mammary lobuloalveolar outgrowth during pregnancy is curtailed

Stat5a^tm1Mam/Stat5a^tm1Mam

        involves: 129S6/SvEvTac

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

Stat5a^tm1Mam/Stat5a^tm1Mam

        C.129S6-Stat5a^tm1Mam

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

Stat5a^tm1Mam/Stat5a^tm1Mam

        involves: 129S6/SvEvTac * C57BL/6

• immune system phenotype
• abnormal spleen cellularity (MGI Ref ID J:112035)
  • exhibit decreased numbers of splenocytes
• decreased NK cell number (MGI Ref ID J:112035)
  • 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
• impaired NK cell cytolysis (MGI Ref ID J:112035)
  • NK cytolytic activity is impaired but to a lesser extent than seen in Stat5b^tm1Hwd homozygotes
• hematopoietic system phenotype
• abnormal spleen cellularity (MGI Ref ID J:112035)
  • exhibit decreased numbers of splenocytes
• decreased NK cell number (MGI Ref ID J:112035)
  • 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

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 and Inflammation Research
Intracellular Signaling Molecules

Stat5a^tm1Mam related

Cancer Research
Genes Regulating Growth and Proliferation

Immunology and Inflammation Research
Immunodeficiency (Mast Cell Deficiency)
Intracellular Signaling Molecules

Research Tools
Immunology and Inflammation Research (Mast Cell Deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Stat5atm1Mam
Allele Name		targeted mutation 1, Lothar Hennighausen
Allele Type		Targeted (knock-out)
Common Name(s)		Stat5a-;
Mutation Made By		Lothar Hennighausen,   National Institutes of Health
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		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, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

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

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 rd; 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]

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]

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]

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

Health & Colony Maintenance Information

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.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.