Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous male mice are sterile due to arrested spermatogenesis at the late meiosis, primary spermatocyte stage. Female homozygotes are fertile. No gene product (mRNA) was detectable by semiquantitative RT-PCR analysis of peripheral nerve. Embryonic testis development is impaired. By six weeks of age, the mass of testes from homozygous males is 90% smaller than testes from heterozygous males. Histological examination reveals a diminished number of germ cells and no mature sperm in the testis or epididymis. Peripheral nerves from mutant mice appear flattened with structurally disorganized protective sheaths. The perineural cells, glia and mesenchymal cells, develop defective tight junctions, causing the perineurium to be permeable. This mutant mouse strain may be useful in studies related to male sterility and regulation of peripheral nerve development.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 1 and 2 and a portion of exon 3, which encode a conserved polypeptide required for protein activity. The construct was electroporated into 129S1/Sv-p+ Tyr+ KitlSl-J/+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts.
|Allele Name||targeted mutation 1, Andrew P McMahon|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Dhh, desert hedgehog|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||Exons 1, 2 and part of 3 were replaced with a neomycin cassette. The deleted segments encode a conserved polypeptide required for protein function. Thus, no functional protein is predicted to be produced from this allele.|
|Mutations Made By|| |
Andrew McMahon, University of Southern California
The resulting mice were crossed at least once to C57BL/6, and have been maintained on a 129 background. The Donating Investigator maintains the strain by crossing homozygous females with heterozygous males. Homozygous males are sterile.
When using the Dhh KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002784 in your Materials and Methods section.