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Interaction between splotch (Sp) and curly tail (ct) mouse mutants in the embryonic development of neural tube
J P Estibeiro1, F A Brook, A J Copp
1Department of Zoology, University of Oxford, UK.
Abstract:
The mouse mutations splotch (Sp) and curly tail (ct) both produce spinal neural tube defects with closely similar morphology, but achieve this by different embryonic mechanisms. To determine whether the mutants may interact during development, we constructed mice carrying both mutations. Double heterozygotes exhibited tail defects in 10% of cases, although the single heterozygotes do not express this phenotype. Backcrosses of double heterozygotes to ct/ct produced offspring with an elevated incidence of neural tube defects, both spina bifida and tail defects, compared with a control backcross in which Sp was not involved. Use of the deletion allele Sp2H permitted embryos carrying a splotch mutation to be recognised by polymerase chain reaction assay. This experiment showed that only embryos carrying Sp2H develop spina bifida in the backcross with ct/ct, suggesting that the genotype Sp2H/+, ct/ct is usually lethal around the time of birth as a result of severe disturbance of neurulation. The interaction between Sp and ct was investigated further by examining embryos in the backcross for developmental markers of the Sp/Sp and ct/ct genotypes. Sp/Sp embryos characteristically lack neural crest derivatives, such as dorsal root ganglia, and die on day 13 of gestation. Double mutant embryos from the backcross did not exhibit either of these characteristics suggesting that homozygosity for ct does not cause Sp/+ embryos to develop as if they were of genotype Sp/Sp. The angle of ventral curvature of the posterior neuropore region is enhanced in affected ct/ct embryos whereas it was found to be reduced in Sp/Sp embryos compared with their normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Mouse mutations splotch (Sp) and curly tail (ct) interact to cause spinal neural tube defects. Double mutants show increased tail and neural tube defects, indicating genetic interaction during embryonic development.
Area of Science:
- Developmental Biology
- Genetics
- Teratology
Background:
- Mouse mutations splotch (Sp) and curly tail (ct) cause similar spinal neural tube defects via distinct embryonic mechanisms.
- Understanding genetic interactions is crucial for deciphering complex developmental pathways.
Purpose of the Study:
- To investigate the developmental interaction between the splotch (Sp) and curly tail (ct) mouse mutations.
- To determine if combined mutations exacerbate neural tube defects.
Main Methods:
- Construction of double heterozygote mice carrying both Sp and ct mutations.
- Backcrossing double heterozygotes with ct/ct mice.
- Utilizing polymerase chain reaction (PCR) with the Sp2H deletion allele for genotyping.
- Analysis of embryonic development and morphological markers.
Main Results:
- Double heterozygotes (Sp/+; ct/+) exhibited tail defects not seen in single heterozygotes.
- Backcrosses revealed an elevated incidence of spina bifida and tail defects in Sp-carrying embryos when combined with ct/ct.
- The genotype Sp2H/+, ct/ct appears to be lethal around birth due to severe neurulation defects.
- Homozygosity for ct did not phenocopy Sp/Sp embryos lacking neural crest derivatives.
Conclusions:
- The splotch and curly tail mutations exhibit genetic interaction during mouse embryonic development.
- This interaction leads to an increased severity and incidence of neural tube and tail defects.
- The combined mutations significantly impact neurulation, suggesting a critical interplay between these genetic factors.