Strain Name:

C.129-Stat5btm1Hwd/J

Stock Number:

007810

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Availability:

Cryopreserved - Ready for recovery

Homozygotes have less adipose tissue than wildtype controls, exhibit abnormal gene expression in liver, reduced insulin-like growth factor 1 (IGF-1) plasma levels, and disrupted urine chemistry. Female homozygotes have impaired lactation, male homozygotes are smaller than wildtype. Some homozygotes develop obesity at approximately 9 weeks of age with large testicular fat pads and increased abdominal fat. This mutant mouse strain may be useful in studies of mammary gland development, lactogenesis and immunological intracellular signal transduction.

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.
Specieslaboratory mouse
GenerationN5pN1
Generation Definitions
 
Donating Investigator Michael Tomasson,   Washington University School of Medicine

Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern and immunoblot analysis of liver, spleen, mammary gland, thymus, kidney or skeletal muscle from homozygous animals. Levels of the closely related Stat5a gene products (mRNA and protein) are unaffected in thymus and spleen. At 4 - 5 weeks of age, male homozygotes are smaller in size and have a reduced body weight (27% lighter than wildtype controls) when compared to wildtype. Female homozygotes exhibit spontaneous abortion between day 8 and 17 of pregnancy and have impaired lactation. Pups (independent of genotype) born to heterozygous females have higher perinatal death than pups born to wildtype females. Some homozygotes have pale and enlarged livers. Homozygotes have less adipose tissue than wildtype controls, exhibit abnormal gene expression in liver, reduced insulin-like growth factor 1 (IGF-1) plasma levels, and disrupted urine chemistry. Male homozygotes have elevated growth hormone plasma levels. Some homozygotes develop obesity at approximately 9 weeks of age with large testicular fat pads and increased abdominal fat. Hair growth is impaired. Homozygotes on the C57BL/6 genetic background (not available from The Jackson Laboratory) have diminished peripheral splenocyte responses to mitogenic stimulation and reduced activated splenocyte proliferation with diminished NK cell number and activity. This mutant mouse strain may be useful in studies of mammary gland development, lactogenesis and immunological intracellular signal transduction.

Development
A targeting vector containing a neomycin resistance cassette and a herpes simplex virus thymidine kinase gene was used to disrupt codon 181. The construct was electroporated into unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to BALB/c mice, and then backcrossed to BALB/cAnNTac for 4 generations using a marker-assisted protocol.

Control Information

  Control
   Wild-type from the colony
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Stat5b
012900   B6.129S6-Stat5a/Stat5btm2Mam/Mmjax
024351   B6N(Cg)-Stat5btm1.1(KOMP)Vlcg/J
View Strains carrying other alleles of Stat5b     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Growth Hormone Insensitivity with Immunodeficiency   (STAT5B)
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.

Stat5btm1Hwd/Stat5btm1Hwd

        involves: C57BL/6
  • immune system phenotype
  • abnormal lymphocyte morphology   (MGI Ref ID J:112035)
    • abnormal double-negative T cell morphology
      • among the double negative cells, there is a moderate decrease in the percentage of CD44+CD25- cells and an increase in the percentage of CD44-CD25+ cells   (MGI Ref ID J:112035)
    • abnormal lymphocyte cell number
      • the T/B cell ratio is slightly decreased   (MGI Ref ID J:112035)
      • decreased CD8-positive T cell number
        • exhibit diminished numbers of single positive splenocytes; the number of CD4-CD8+ splenocytes is reduced, whereas, the number of CD4+CD8- cells is only slightly affected   (MGI Ref ID J:112035)
      • decreased NK cell number
        • percentage of NK (CD3-DX5+) cells is diminished (about 55% of the percentage seen in wild-type)   (MGI Ref ID J:112035)
        • exhibit a decrease in IL2-Rbeta+ NK cells   (MGI Ref ID J:112035)
      • decreased thymocyte number
        • thymocyte numbers are modestly diminished   (MGI Ref ID J:112035)
    • decreased T cell proliferation
      • splenocytes exhibit greatly diminished proliferation in response to IL-2 and IL-15 and a combination of PMA and IL-4   (MGI Ref ID J:112035)
  • decreased splenocyte number
    • exhibit decreased numbers of splenocytes in the periphery   (MGI Ref ID J:112035)
  • impaired natural killer cell mediated cytotoxicity
    • NK cytolytic activity is impaired   (MGI Ref ID J:112035)
  • hematopoietic system phenotype
  • abnormal lymphocyte morphology   (MGI Ref ID J:112035)
    • abnormal double-negative T cell morphology
      • among the double negative cells, there is a moderate decrease in the percentage of CD44+CD25- cells and an increase in the percentage of CD44-CD25+ cells   (MGI Ref ID J:112035)
    • abnormal lymphocyte cell number
      • the T/B cell ratio is slightly decreased   (MGI Ref ID J:112035)
      • decreased CD8-positive T cell number
        • exhibit diminished numbers of single positive splenocytes; the number of CD4-CD8+ splenocytes is reduced, whereas, the number of CD4+CD8- cells is only slightly affected   (MGI Ref ID J:112035)
      • decreased NK cell number
        • percentage of NK (CD3-DX5+) cells is diminished (about 55% of the percentage seen in wild-type)   (MGI Ref ID J:112035)
        • exhibit a decrease in IL2-Rbeta+ NK cells   (MGI Ref ID J:112035)
      • decreased thymocyte number
        • thymocyte numbers are modestly diminished   (MGI Ref ID J:112035)
    • decreased T cell proliferation
      • splenocytes exhibit greatly diminished proliferation in response to IL-2 and IL-15 and a combination of PMA and IL-4   (MGI Ref ID J:112035)
  • decreased splenocyte number
    • exhibit decreased numbers of splenocytes in the periphery   (MGI Ref ID J:112035)
  • impaired natural killer cell mediated cytotoxicity
    • NK cytolytic activity is impaired   (MGI Ref ID J:112035)

Stat5btm1Hwd/Stat5btm1Hwd

        involves: 129 * BALB/c
  • adipose tissue phenotype
  • decreased total body fat amount
    • both males and females exhibit less adipose tissue   (MGI Ref ID J:41784)
    • weight of sublumbar adipose tissue in females is reduced to 36% of wild-type and to 69% of wild-type in males   (MGI Ref ID J:41784)
  • endocrine/exocrine gland phenotype
  • abnormal lactation
    • produce insufficient milk to feed pups   (MGI Ref ID J:41784)
  • abnormal mammary gland development
    • mammary gland development is impaired although milk proteins are expressed   (MGI Ref ID J:41784)
  • growth/size/body phenotype
  • decreased body weight
    • males, but not females, show decreased body weight so that by 4-5 weeks of age, males are 27% lighter than wild-type and this difference persists beyond puberty   (MGI Ref ID J:41784)
  • decreased total body fat amount
    • both males and females exhibit less adipose tissue   (MGI Ref ID J:41784)
    • weight of sublumbar adipose tissue in females is reduced to 36% of wild-type and to 69% of wild-type in males   (MGI Ref ID J:41784)
  • obese
    • obesity becomes apparent in some mutants beginning at about 9 weeks of age, showing large testicular fat pads and greater amounts of abdominal fat   (MGI Ref ID J:41784)
  • homeostasis/metabolism phenotype
  • decreased circulating insulin-like growth factor I level
    • plasma IGF-1 concentrations are lower in both males and females   (MGI Ref ID J:41784)
  • decreased urine major urinary protein level
    • MUP, a family of alpha2-microglobulin-related liver secretory proteins that comprise a major protein component of mouse urine, levels in male urine are similar to the amounts seen in female urine which is less than seen in wild-type males   (MGI Ref ID J:41784)
  • increased circulating growth hormone level
    • males, but not females, exhibit normal to elevated plasma growth hormone levels   (MGI Ref ID J:41784)
  • liver/biliary system phenotype
  • abnormal liver physiology
    • male-specific liver gene expression is decreased to wild-type female levels in homozygous males, while female-predominant liver gene products are increased in males to a level intermediate between wild-type male and female levels   (MGI Ref ID J:41784)
  • enlarged liver
    • seen in some homozygotes   (MGI Ref ID J:41784)
  • pale liver
    • seen in some homozygotes   (MGI Ref ID J:41784)
  • renal/urinary system phenotype
  • decreased urine major urinary protein level
    • MUP, a family of alpha2-microglobulin-related liver secretory proteins that comprise a major protein component of mouse urine, levels in male urine are similar to the amounts seen in female urine which is less than seen in wild-type males   (MGI Ref ID J:41784)
  • reproductive system phenotype
  • abnormal spontaneous abortion rate
    • females consistently abort between day 8 and 17 of pregnancy, with no obvious maternal, placental or fetal defects; deaths are not associated with genotype of pups   (MGI Ref ID J:41784)
    • subcutaneous administration of progesterone maintains pregnancy   (MGI Ref ID J:41784)
  • integument phenotype
  • abnormal hair growth
    • exhibit a delay of at least 2 weeks in the commencement of second-generation hair growth   (MGI Ref ID J:41784)
    • sparse hair
      • seen in some homozygotes   (MGI Ref ID J:41784)
  • abnormal lactation
    • produce insufficient milk to feed pups   (MGI Ref ID J:41784)
  • abnormal mammary gland development
    • mammary gland development is impaired although milk proteins are expressed   (MGI Ref ID J:41784)
View Research Applications

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

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)

Endocrine Deficiency Research
Adipose Defects
Mammary Gland Defects

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Stat5btm1Hwd
Allele Name targeted mutation 1, Helen W Davey
Allele Type Targeted (knock-out)
Common Name(s) STAT5b-; Stat5b KO;
Mutation Made By Michael Tomasson,   Washington University School of Medicine
Gene Symbol and Name Stat5b, signal transducer and activator of transcription 5B
Chromosome 11
Gene Common Name(s) STAT5;
Molecular Note The gene was disrupted by insertion of a neomycin resistance cassette into codon 181 via homologous recombination. Absence of gene expression in liver, spleen, mammary gland, thymus, kidney, and skeletal muscle of homozygous mutant animals was demonstrated by Northern and Western blot analyses. [MGI Ref ID J:41784]

Genotyping

Genotyping Information

Genotyping Protocols

Stat5btm1Hwd, Melt Curve Analysis
Stat5btm1Hwd, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Udy GB; Towers RP; Snell RG; Wilkins RJ; Park SH; Ram PA; Waxman DJ ; Davey HW. 1997. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci U S A 94(14):7239-44. [PubMed: 9207075]  [MGI Ref ID J:41784]

Additional References

Stat5btm1Hwd related

Bennett E; McGuinness L; Gevers EF; Thomas GB; Robinson IC; Davey HW; Luckman SM. 2005. Hypothalamic STAT proteins: regulation of somatostatin neurones by growth hormone via STAT5b. J Neuroendocrinol 17(3):186-94. [PubMed: 15796771]  [MGI Ref ID J:110149]

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]

Davey HW; Park SH; Grattan DR; McLachlan MJ; Waxman DJ. 1999. STAT5b-deficient mice are growth hormone pulse-resistant. Role of STAT5b in sex-specific liver p450 expression. J Biol Chem 274(50):35331-6. [PubMed: 10585399]  [MGI Ref ID J:58893]

Davey HW; Xie T; McLachlan MJ; Wilkins RJ; Waxman DJ; Grattan DR. 2001. STAT5b is required for GH-induced liver IGF-I gene expression. Endocrinology 142(9):3836-41. [PubMed: 11517160]  [MGI Ref ID J:71045]

Grattan DR; Xu J; McLachlan MJ; Kokay IC; Bunn SJ; Hovey RC; Davey HW. 2001. Feedback regulation of PRL secretion is mediated by the transcription factor, signal transducer, and activator of transcription 5b. Endocrinology 142(9):3935-40. [PubMed: 11517172]  [MGI Ref ID J:71889]

Holloway MG; Laz EV; Waxman DJ. 2006. Codependence of growth hormone-responsive, sexually dimorphic hepatic gene expression on signal transducer and activator of transcription 5b and hepatic nuclear factor 4alpha. Mol Endocrinol 20(3):647-60. [PubMed: 16239260]  [MGI Ref ID J:105869]

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]

Laz EV; Holloway MG; Chen CS; Waxman DJ. 2007. Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. Endocrinology 148(7):3327-37. [PubMed: 17412818]  [MGI Ref ID J:129617]

Li J. 2013. JAK-STAT and bone metabolism. JAKSTAT 2(3):e23930. [PubMed: 24069548]  [MGI Ref ID J:202463]

Oldham JM; Osepchook CC; Jeanplong F; Falconer SJ; Matthews KG; Conaglen JV; Gerrard DF; Smith HK; Wilkins RJ; Bass JJ; McMahon CD. 2009. The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone. J Physiol 587(Pt 3):669-77. [PubMed: 19047209]  [MGI Ref ID J:176556]

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]

Yamaji D; Kang K; Robinson GW; Hennighausen L. 2013. Sequential activation of genetic programs in mouse mammary epithelium during pregnancy depends on STAT5A/B concentration. Nucleic Acids Res 41(3):1622-36. [PubMed: 23275557]  [MGI Ref ID J:200216]

Zhou YC; Davey HW; McLachlan MJ; Xie T; Waxman DJ. 2002. Elevated basal expression of liver peroxisomal beta-oxidation enzymes and CYP4A microsomal fatty acid omega-hydroxylase in STAT5b(-/-) mice: cross-talk in vivo between peroxisome proliferator-activated receptor and signal transducer and activator of transcription signaling pathways. Toxicol Appl Pharmacol 182(1):1-10. [PubMed: 12127257]  [MGI Ref ID J:110713]

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 & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Male homozgotes have a growth defect and female homozygotes have a milk production defect.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000651 BALB/cJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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