Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis. Homozygous female mice are fertile. Homozygous male mice are subfertile, producing small litters. Sperm retention in seminiferous tubules of mutant mice is due to increased sperm tail abnormalities. Transition protein 1 and precursor and partially processed protamine 2 levels are elevated in testis tissue. Electron microscopy analysis of mutant testis tissue reveals abnormal cylindrical focal chromatin condensation morphology in spermatids and incomplete chromatin condensation with lacunae and granularity in late stage spermatids and epididymal sperm. Increased uptake of DNA intercalating dyes by mutant sperm nuclei and susceptibility of mutant sperm DNA to acid denaturation is indicative of DNA strand breakage. This mutant mouse strain may be useful in studies of male infertility and/or subfertility.
A targeting vector containing a neomycin resistance gene flanked by loxP sites and a herpes simplex virus thymidine kinase genes was used to disrupt the entire targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt+ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.
|Allele Name||targeted mutation 1, Ming Zhao|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tnp2, transition protein 2|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||The entire gene was replaced with a neo cassette flanked by loxP sites via homologous recombination. Northern and Western blot analysis verified the absence of gene expression in testes of homozygous mutant animals.|
|Mutations Made By|| |
Dr. Marvin Meistrich, University of Texas M.D. Anderson Cancer
The resulting male chimeric animals were crossed to 129S6/SvEvTac females. This strain is maintained as heterozygous males and homozygous females.
When using the Tnp2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004514 in your Materials and Methods section.