This spontaneous mutation provides a model for autosomal recessive osteopetrosis 2. Homozygotes have significant osteopetrosis, craniofacial deformities, failure of tooth eruption, smaller body size, reduced fertility and, in a few homozygotes, muscular dystrophy.Read More +
Mice homozygous for the gummy intragenic inversion have osteopetrotic bone development with dramatically denser bones, filled medullary spaces in the long bones, failed tooth eruption, and a much smaller overall body size. The skulls are severely effected with highly thickened bone, high levels of ossification in the hyoid and zygomatic arches, absent maxillary-premaxillary sutures, severely misshapen mandible, and what appears to be an additional tooth in the area of the mandibular foramina even though the teeth fail to erupt. As a result the head is misshapen. Whole body areal bone mineral density is significantly higher. Some homozygotes develop facial abscesses, and a few homozygotes have histologic signs of dystrophic muscle, with small muscle fibers and evidence of muscle fiber degeneration and regeneration. Tail length is proportionally shorter. Homozygous males have reduced fertility possibly due to decreased sperm motility, and pups born to homozygous females all die within a day of birth, likely due to failure of females to lactate, which is suggested by the absence of a milk spot. Heterozygotes are viable and fertile.
The gummy intragenic inversion arose spontaneously in STOCK Tg(Myh6-cre)1Jmk/J at The Jackson Laboratory. That strain was a mix of FVB, C57BL/6J, and C3H/HeJ. The mutant sub-strain was outcrossed once to C57BL/6J to remove the transgene and subsequently maintained by sibling intercrossing heterozgyotes. Sperm was cryopreserved from homozygous males and standard cryorecovery is scheduled to use C57BL/6J oocytes.
|Allele Type||Spontaneous (Null/Knockout)|
|Gene Symbol and Name||Tnfsf11, tumor necrosis factor (ligand) superfamily, member 11|
|Strain of Origin||STOCK Tg(Myh6-cre)1Jmk/J|
|Molecular Note||A spontaneous 4.7 kb inversion from Chromosome 14 78,279,775 bp to 78,284,475 bp (GRCm38/mm10) has breakpoints in the introns between exons 2 and 3 and 4 and 5, leaving the exons intact but exons 3 and 4 inverted.|
Homozygous males have low sperm motility and pups born to homozygous females all die within a day of birth, likely due to failure of females to lactate as evidenced by the absence of a milk spot. While some homozygous males have produced one or two litters, this strain is best maintained through heterozygous intercrossing.
When using the gummy mouse strain in a publication, please cite the originating article(s) and include JAX stock #025121 in your Materials and Methods section.