Homozygous Mybl1 (A-myb) knockout mice demonstrate male fertility defects, female mammary gland defects post pregnancy, and impaired serum antibody responses.
E. P. Reddy, Mount Sinai School of Medicine
Mybl1 (myeloblastosis oncogene-like 1; also called A-myb) encodes a nuclear protein that binds DNA in a sequence-specific manner and functions as a regulator of transcription. Expression of the protooncogene is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles.
These mice carry a targeted knockout of the mouse gene. Northern blot analysis of testicular tissue shows normal levels of transcript in heterozygous mice, but no transcript is detected in homozygous mutant mice. Western blot analysis using a polyclonal antibody directed against the DNA binding domain confirms the absence of normal protein in homozygous mutant mice. Homozygous animals develop to term, but show defects in growth after birth, and reduced viability. Homozygous males are infertile due to a block in spermatogenesis. Germ cells in the male testes enter meiotic prophase and arrest at the pachytene stage. Adult female homozygotes show underdevelopment of breast tissue following pregnancy, and are unable to nurse their newborn pups. Fostering is an option. Homozygous mice are generally less viable, smaller than littermates and can appear hyperactive and more aggressive (especially males).
Homozygotes also display mild splenic white pulp hypoplasia and blunted primary serum antibody responses. Although the gene is not directly involved in regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.
A neomycin resistance cassette was introduced to exon 4 via homologous recombination in embryonic stem (ES) cells to disrupt the DNA binding domain. This strain was backcrossed to C57BL/6 for 10 generations by the donating lab.
|Allele Name||targeted mutation 1, E Premkumar Reddy|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mybl1, myeloblastosis oncogene-like 1|
|Strain of Origin||Not Specified|
|Molecular Note||The DNA binding domain encoded by the endogenous locus was disrupted by the insertion of a neomycin selection cassette into exon 4. While Northern blot analysis of testicular tissue showed normal levels of transcript in heterozygous mice, no transcript was detected in homozygous mutant mice. Western blot analysis using a polyclonal antibody directed against the DNA binding domain confirmed the absence of normal protein in homozygous mutant mice.|
Homozygous males have defective spermatogenesis and are infertile. Sperm count is reduced in heterozygotes. Homozygous females can become pregnant but are unable to nurse their young due to defective mammary development and possible behavioral issues (no nesting of pups). Fostering is an option. Homozygous mice are generally less viable, smaller than littermates and can appear hyperactive and more aggressive (especially males).
When using the A-myb-/- mouse strain in a publication, please cite the originating article(s) and include JAX stock #027748 in your Materials and Methods section.
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