Related Experiment Videos
Retinoic acid-induced selective mortality of splotch-delayed mouse neural tube defect mutants
1Department of Biology, McGill University, Montreal, Quebec, Canada.
Abstract:
The allelic loci splotch (Sp) and splotch-delayed (Spd) cause neural tube defects (NTDs) in mice homozygous for either of these genes. The polymorphic enzyme isocitrate dehydrogenase (Idh-1) in conjunction with a recombination suppressor was used as a genetic marker to identify embryos homozygous for these alleles. A split dose of all-trans retinoic acid (RA) totalling 5.0 mg/kg administered on gestation day 9/15 and 9/18 (days/h) significantly reduced the frequencies of NTD and of mutant genotypes in marked Spd embryos examined on day 16 without significantly increasing the resorption frequency. There was a nonsignificant decrease in the frequencies of NTD and mutant genotypes in embryos examined on day 11 of gestation. Thus, retinoic acid treatment was associated with selective mortality of the homozygous Spd mutants. No evidence of selective mortality was observed in RA-treated Sp embryos.
Insights
Retinoic acid treatment significantly reduced neural tube defects (NTDs) and mutant genotypes in splotch-delayed (Spd) mouse embryos. This suggests retinoic acid causes selective mortality in homozygous Spd mutants.
Area of Science:
- Developmental biology
- Genetics
- Teratology
Background:
- Allelic loci splotch (Sp) and splotch-delayed (Spd) are known to cause neural tube defects (NTDs) in homozygous mice.
- Identifying embryos with these mutations requires specific genetic markers.
Purpose of the Study:
- To investigate the effect of all-trans retinoic acid (RA) on the frequency of NTDs and mutant genotypes in Sp and Spd mouse embryos.
- To determine if RA treatment influences the survival of homozygous Spd mutants.
Main Methods:
- A split dose of all-trans retinoic acid (RA) was administered to pregnant mice on specific gestation days.
- Genetic markers, including isocitrate dehydrogenase (Idh-1), were used to identify homozygous mutant embryos.
- Embryos were examined at different gestational stages (day 11 and day 16) to assess NTD frequency and genotype.
Main Results:
- RA treatment significantly reduced NTDs and mutant genotypes in Spd embryos by day 16 without increasing resorption.
- A nonsignificant decrease in NTDs and mutant genotypes was observed in Spd embryos by day 11.
- No evidence of selective mortality was found in RA-treated Sp embryos.
Conclusions:
- All-trans retinoic acid treatment is associated with selective mortality of homozygous Spd mutants.
- RA may offer a therapeutic avenue for managing certain genetic forms of neural tube defects.