This spontaneous 2 base pair deletion provides a viable recessive allele, which causes thyroid defects, neovascular retinaopathy, sperm defects, and hair cell loss in the crista ampullaris and organ of Corti, phenotypes that are distinct from those of a targeted disruption that causes homozygous embryonic lethal before implantation. This allele is valuable in characterizing this component of the AP-1 complex.Read More +
The recessive figure eight mutation causes thyroid defects, neovascular retinaopathy, sperm defects, and hair cell loss in the crista ampullaris and organ of Corti. Homozygotes display head tilting and circling behaviors and an inability to orient in water to swim. By one month of age ABR thresholds are elevated by approximately 40 dB across all frequencies, and by six months of age homozygotes have no detectable ABR, even at 100 dB. Histology of the inner ears at one month of age found no cochlear abnormalities, but by three months of age there is complete degeneration of the organ of Corti. Scanning electron microscopy of the organ of Corti at 5 weeks of age revealed the absence of some outer hair cell bundles, greatest near the apex and base, but normal inner hair cells and normal orientation and patterning of hair cells. Vestibular hair cell loss was also found in cross sections of the crista ampullaris. Scattered depigmented spots of the retina are found at 6 weeks of age, which develop into large depigmented areas by 16 weeks of age and newly formed vessels are found in the retina at both time points. Choroidal neovascularization with leakage was found by fluorescein angiography. Despite these defects, electroretinaograms showed normal amplitudes at 16 weeks of age. Homozygotes also have thyroid defects, with only a few normal follicles and many highly proliferating epithelial cells found at 15 weeks of age. Serum T4 levels are lower than normal, and homozygotes have a reduced body size, with females weighing an average of 5.9g less and males 3g less than controls between 4 and 6 weeks of age. Homozygous males have reduced fertility, but do reproduce. The germinal epithelium of the testes is disorganized, there are fewer maturing sperm cells, reduced total concentration of spermatozoa, and reduced sperm motility, with nearly half of the mature spermatozoa having their tail bent at the mid-piece. Nevertheless, all meiotic stages are present in the seminiferous tubules.
The figure eight mutation arose spontaneously at The Jackson Laboratory in the strain C57BL/6-Tg(APOA1)1Rub/J and a mutant was bred to C57BL/6J and genotyped to select against Tg(APOA1)1Rub. One additional backcross to C57BL/6J was done before the strain was maintained by sibling breeding heterozygous females with, primarily, homozygous males.
|Allele Name||figure eight|
|Allele Type||Spontaneous (Hypomorph)|
|Gene Symbol and Name||Ap1g1, adaptor protein complex AP-1, gamma 1 subunit|
|Strain of Origin||C57BL/6-Tg(APOA1)1Rub/J|
|Molecular Note||This spontaneous 6 bp deletion of TTTCTG in exon 13 of NM009677, isoform 1, and exon 12 of Nm002301211, isoform 2, is predicted to cause an in-frame deletion of F391 and L392 of isoform 1, or F388 and L389 of isoform 2, amino acids which are in the adaptin N-terminal homology domain involved in interactions with other subunitos of the AP-1 complex.|
Although homozygous males have reduced fertility, they are generally adequate breeders to maintain a colony. Cryopreserved sperm from homozygous males has failed in in vitro fertilization efforts. Because the spinning of the homozygote can interfere with the rearing of the pups it is best to remove the homozygous male before birth and if homozygous females are used for breeding it is best to foster the pups.
When using the C57BL/6-Ap1g1fgt/KjnBoc mouse strain in a publication, please cite the originating article(s) and include JAX stock #006487 in your Materials and Methods section.