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Disruption of Apc10/Doc1 in three alleles of oligosyndactylism
1Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA. pravtcdd@sprintmail.com
Abstract:
Oligosyndactylism (Os) is a radiation-induced mouse mutation associated with recessive lethality and a dominant effect on limb and kidney development. The lethal effect of the mutation is due to a cell-autonomous block in the transition from metaphase to anaphase. We have previously characterized two transgene-induced mutations, 94-A and 94-K, which are allelic with Os. These mutations facilitated the identification of genomic segments and transcribed sequences in the affected region. One of the transcripts in this region corresponds to the mouse homolog of the anaphase-promoting complex component APC10/DOC1. The disruption of this gene can explain the mitotic arrest phenotype of all three alleles of Os.
Insights
Oligosyndactylism (Os) is a radiation-induced mutation causing developmental defects and lethality. Disruption of the APC10/DOC1 gene explains the mitotic arrest observed in Os mice.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Oligosyndactylism (Os) is a radiation-induced mutation in mice.
- It exhibits recessive lethality and dominant effects on limb and kidney development.
- The lethal phenotype is linked to a cell-autonomous block in metaphase-to-anaphase transition.
Purpose of the Study:
- To identify the genetic basis of Oligosyndactylism (Os).
- To understand the molecular mechanisms underlying the observed developmental defects and lethality.
- To investigate the role of the anaphase-promoting complex in Os.
Main Methods:
- Characterization of two transgene-induced mutations (94-A and 94-K) allelic to Os.
- Identification of genomic segments and transcribed sequences in the affected region.
- Analysis of the mouse homolog of anaphase-promoting complex component APC10/DOC1.
Main Results:
- Two transgene-induced mutations, 94-A and 94-K, were found to be allelic with Os.
- Genomic analysis identified candidate genes within the Os-affected region.
- A transcript corresponding to the mouse homolog of APC10/DOC1 was identified in this region.
Conclusions:
- The disruption of the APC10/DOC1 gene is the likely cause of the Oligosyndactylism (Os) mutation.
- This gene disruption explains the mitotic arrest phenotype observed in Os alleles.
- APC10/DOC1 plays a critical role in cell cycle progression and development.