This mutant is valuable for the study of fluid homeostasis in the inner ear and kidney. Mutations in ATP6V1B1 cause the human genetic disease distal renal tubular acidosis with progressive nerve deafness. On the MRL/MpJ inbred background vortex homozygotes have inner ear defects that are not found in C57BL/6J congenic vortex homozygotes. On both backgrounds this mutation causes hypocalciuria, with greater severity on the MRL/MpJ background, but increased urine pH is only found on the C57BL/6J background, possibly due to the inherently high urine pH of the MRL/MpJ inbred strain.Read More +
The vortex mutation is a spontaneous point mutation causing a G78D amino acid substitution in Atp6v1b1, a component of the vacuolar H+ ATPase pump that is active in the kidneys and inner ear. Mutations in the human ortholog, including two separate instances of G78D substitutions, have been shown to cause distal renal tubular acidosis with progressive nerve deafness (OMIM #267300). While vortex homozygotes on either the MRL/MpJ or C57BL/6J background have normal potassium, sodium, and chloride concentrations in blood and urine, both show decreased calcium in the urine, with only 45.9 +/- 6.01 mg/g in MRL/MpJ homozygotes relative to 163.3 +/- 17.4 mg/g in MRL/MpJ controls, a reduction of approximately 70%, and 99 +/- 9.6 mg/g in C57BL/6J congenic homozygotes versus 139.2 +/- 9.1 in C57BL/6J controls, a reduction of approximately 30%. No elevation in urine pH was found on the MRL background (see Stock No. 021771), but the MRL/MpJ inbred strain has a naturally high urine pH relative to other inbred strains. On the C57BL/6J congenic background an elevation in urine pH is found, but the inner ear develops normally and ABR thresholds and measurements of endocochlear potential are normal. However, on the MRL/MpJ background vortex homozygotes developmental defects of the inner ear with profound hearing and vestibular impairment, likely the result of failed fluid homeostasis. No abnormal phenotypes have been identified in heterozygotes on either inbred genetic background. (Tian et al., 2017.)
A homozygous MRL/MpJ-Atp6v1b1vtx/Kjn male at generation N6F8 was bred to a C57BL/6J female and through repeated backcrossing of genotyped heterozygotes to C57BL/6J this congenic strain was generated. When this congenic reached N10 it was sibling intercrossed to homozygosity and subsequently maintained by intercrossing homozygotes. In 2017 this strain reached generation N10F5.
|Allele Type||Spontaneous (Not Specified)|
|Gene Symbol and Name||Atp6v1b1, ATPase, H+ transporting, lysosomal V1 subunit B1|
|Strain of Origin||MRL/MpJ-Faslpr/J|
|Molecular Note||This spontaneous G to A transition in exon 3 (c.233G>A) replaces a highly conserved glycine with an aspartic acid at amino acid 78 in the amino terminal domain.|