These Stat5a knock-out mice exhibit reduction in lobuloalveolar development with no milk secretion even after prolonged suckling.
IMR Colony, The Jackson Laboratory
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.
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.
|Allele Name||targeted mutation 1, Lothar Hennighausen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Stat5a, signal transducer and activator of transcription 5A|
|Strain of Origin||129S6/SvEvTac|
|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.|
|Mutations Made By|| |
Dr. Lothar Hennighausen, National Institutes of Health
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.
When using the Stat5a KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003502 in your Materials and Methods section.