C.129S(B6)-Stat5a^tm1Mam/J

Stock number: 007806
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Mice that are homozygous for this 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. This mutant mouse strain may be useful in studies of mammary gland development, cancer research and immunological intracellular signal transduction.

Detailed description

Mice homozygous for the targeted mutation are viable, develop normally, and are fertile, but females do not lactate. Mammary ductal development through pregnancy is normal, but lobuloalveolar development is severely reduced, and milk is not secreted even after prolonged suckling. Levels of the closely-related STAT5B protein are also markedly reduced in STAT5A-deficient mice, but STAT5B protein levels increase and phosphorylation is evident after 3 days of suckling. Expression of several milk protein genes is unaffected in homozygous mutants, but 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 casette 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, and correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to 129 mice, and then backcrossed to C57BL/6 for one generation. The donating investigator backcrossed the strain to BALB/cAnNTac for 3 generations using a marker-assisted protocol. The mice were subsequently backcrossed to BALB/cJ for a single generation.

Allele

Symbol: Stat5a^tm1Mam
Name: targeted mutation 1, Lothar Hennighausen
MGI accession ID: MGI:1857249
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Stat5a
Marker name: signal transducer and activator of transcription 5A
Chromosome: 11
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.