Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome.
The transcription factor TBX3 plays critical roles in development and TBX3 mutations in humans cause Ulnar-mammary syndrome. Efforts to understand how altered TBX3 dosage and function disrupt the development of numerous structures have been hampered by embryonic lethality of mice bearing presumed nu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3699485?pdf=render |
| _version_ | 1819078539825119232 |
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| author | Deborah U Frank Uchenna Emechebe Kirk R Thomas Anne M Moon |
| author_facet | Deborah U Frank Uchenna Emechebe Kirk R Thomas Anne M Moon |
| author_sort | Deborah U Frank |
| collection | DOAJ |
| description | The transcription factor TBX3 plays critical roles in development and TBX3 mutations in humans cause Ulnar-mammary syndrome. Efforts to understand how altered TBX3 dosage and function disrupt the development of numerous structures have been hampered by embryonic lethality of mice bearing presumed null alleles. We generated a novel conditional null allele of Tbx3: after Cre-mediated recombination, no mRNA or protein is detectable. In contrast, a putative null allele in which exons 1-3 are deleted produces a truncated protein that is abnormally located in the cytoplasm. Heterozygotes and homozygotes for this allele have different phenotypes than their counterparts bearing a true null allele. Our observations with these alleles in mice, and the different types of TBX3 mutations observed in human ulnar-mammary syndrome, suggest that not all mutations observed in humans generate functionally null alleles. The possibility that mechanisms in addition to TBX3 haploinsufficiency may cause UMS or other malformations merits investigation in the human UMS population. |
| first_indexed | 2024-12-21T19:14:42Z |
| format | Article |
| id | doaj.art-961d5a3a701f45c48bc5c7022bfd16fb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T19:14:42Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-961d5a3a701f45c48bc5c7022bfd16fb2022-12-21T18:53:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6784110.1371/journal.pone.0067841Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome.Deborah U FrankUchenna EmechebeKirk R ThomasAnne M MoonThe transcription factor TBX3 plays critical roles in development and TBX3 mutations in humans cause Ulnar-mammary syndrome. Efforts to understand how altered TBX3 dosage and function disrupt the development of numerous structures have been hampered by embryonic lethality of mice bearing presumed null alleles. We generated a novel conditional null allele of Tbx3: after Cre-mediated recombination, no mRNA or protein is detectable. In contrast, a putative null allele in which exons 1-3 are deleted produces a truncated protein that is abnormally located in the cytoplasm. Heterozygotes and homozygotes for this allele have different phenotypes than their counterparts bearing a true null allele. Our observations with these alleles in mice, and the different types of TBX3 mutations observed in human ulnar-mammary syndrome, suggest that not all mutations observed in humans generate functionally null alleles. The possibility that mechanisms in addition to TBX3 haploinsufficiency may cause UMS or other malformations merits investigation in the human UMS population.http://europepmc.org/articles/PMC3699485?pdf=render |
| spellingShingle | Deborah U Frank Uchenna Emechebe Kirk R Thomas Anne M Moon Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. PLoS ONE |
| title | Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. |
| title_full | Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. |
| title_fullStr | Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. |
| title_full_unstemmed | Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. |
| title_short | Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome. |
| title_sort | mouse tbx3 mutants suggest novel molecular mechanisms for ulnar mammary syndrome |
| url | http://europepmc.org/articles/PMC3699485?pdf=render |
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