PloS one, 2013-07, Vol.8 (7), p.e67841-e67841
2013
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- Autor(en) / Beteiligte
- Titel
- Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome
- Ist Teil von
- PloS one, 2013-07, Vol.8 (7), p.e67841-e67841
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0067841Titel-ID: cdi_plos_journals_1426970606
- Format
- –
- Schlagworte
- Abnormalities, Multiple - embryology, Abnormalities, Multiple - genetics, Abnormalities, Multiple - metabolism, Alleles, Animals, Biology, Breast, Breast Diseases - embryology, Breast Diseases - genetics, Breast Diseases - metabolism, Cre recombinase, Cysts, Cytoplasm, Defects, Development and progression, Embryogenesis, Exons, Female, Fibrocystic breast disease, Gene expression, Gene Expression Regulation, Developmental, Gene mutations, Genetic aspects, Genetics, Genotype, Haploinsufficiency, Heart - embryology, Heterozygotes, Hindlimb - abnormalities, Hindlimb - embryology, Hindlimb - metabolism, Homozygotes, Humans, Immunohistochemistry, Lethality, Male, Medicine, Mice, Mice, 129 Strain, Mice, Inbred Strains, Mice, Knockout, Molecular modelling, Mutants, Mutation, Myocardium - metabolism, Myocardium - pathology, Neurobiology, Neurosciences, Pediatrics, Physiological aspects, Proteins, Recombination, Reverse Transcriptase Polymerase Chain Reaction, T-Box Domain Proteins - genetics, T-Box Domain Proteins - metabolism, Transcription factors, Ulna - abnormalities, Ulna - embryology, Ulna - metabolism