<i>Dach1</i> Mutant Mice Bear No Gross Abnormalities in Eye, Limb, and Brain Development and Exhibit Postnatal Lethality

Davis, R. J.; Shen, Weiping; Sandler, Yakov I.; Amoui, Mehran; Purcell, Patricia; Maas, Richard L.; Ou, Ching-Nan; Vogel, Hannes; Beaudet, Arthur L.; Mardon, Graeme

doi:10.1128/mcb.21.5.1484-1490.2001

Cited by 96 publications

(59 citation statements)

References 42 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, all homozygous null mutant mice died (n ϭ 5) within 24 hr after birth. This finding is in accordance with the data of Davis et al (2001a). In contrast to wild-type and heterozygous litter mates, stomachs of the majority but not all of null mutants (11 of 13) were found empty of milk.…”

Section: Homozygous Null Micesupporting

confidence: 82%

“…In humans, Dach1 maps to chromosome13q21.1, a locus that is associated with mental retardation and skeletal abnormalities (Caubit et al, 1999), but mutations in Dach1 have not been hitherto shown to correlate with any developmental disorders (Ayres et al, 2001). Although redundancy of Dach genes in vertebrates had been hypothesized, a recent report by Davis et al (2001a) documents that Dach1 homozygous null mice die at birth. This finding indicates that at least some essential functions in the organism require a functional Dach1.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted disruption of mouse Dach1 results in postnatal lethality

Backman

Machoň

Bout

et al. 2002

Developmental Dynamics

View full text Add to dashboard Cite

Mouse Dach1 is a nuclear factor that is expressed during development in restricted areas of the central nervous system, neural crest, and limb buds. Its Drosophila homologue dachshund plays a role in differentiation of the eye imaginal disc, in leg morphogenesis, and in controlling neural differentiation in the mushroom bodies of the insect brain. Mouse Dach1 null homozygous survive pregnancy but become cyanotic after birth and subsequently die within 24 hr. In this report, the brain of

show abstract

Section: Homozygous Null Micesupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Targeted disruption of mouse Dach1 results in postnatal lethality

Backman

Machoň

Bout

et al. 2002

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…In both vertebrates and invertebrates dachshund displays a complex temporal and spatial pattern of expression, and the gene product is critical in the development of the central nervous system, sensory organs, and limbs [19][20][21][22]23].…”

Section: Introductionmentioning

confidence: 99%

In vivo characterization of a vertebrate ultraconserved enhancer

et al. 2005

View full text Add to dashboard Cite

Genomic sequence comparisons between human, mouse and pufferfish (Takifugu rubripes (Fugu)) have revealed a set of extremely conserved noncoding sequences. While this high degree of sequence conservation suggests severe evolutionary constraint and predicts a lack of tolerance to change in order to retain in vivo functionality, such elements have been minimally explored experimentally. In this study, we describe the in-depth characterization of an ancient conserved enhancer, Dc2 located near the dachshund gene, which displays a human-Fugu identity of 84% over 424 basepairs (bp). In addition to this large overall conservation, we find that Dc2 is characterized by the presence of a large block of sequence (144 bp) that is completely identical between human, mouse, chicken, zebrafish and Fugu. Through the testing of reporter vector constructs in transgenic mice, we observed that the 424 bp Dc2 conserved element is necessary and sufficient for brain tissue enhancer activity. In vivo analyses also revealed that the 144 bp 100% conserved sequence is necessary, but not sufficient, to replicate Dc2 enhancer function. However, the introduction of two separate 16 bp insertions into the highly conserved enhancer core did not cause any detectable modification of its in vivo activity. Our observations indicate that the 144 bp 100% conserved element is tolerant of change at least at the resolution of this transgenic mouse assay and suggest that purifying selection on Dc2 sequence might not be as strong as we predicted or that some unknown property also constrains this highly conserved enhancer sequence. Thank you for your letter of February 15 th and for the reviewers' comments on our manuscript entitled "In Vivo Characterization of a Vertebrate Ultra-conserved Enhancer", by Poulin et al. We have addressed the reviewers' concerns in a revised manuscript, which we are resubmitting for your consideration.Our detailed response is as follows:Reviewer #21. Abstract -last sentence should read: "tolerant of change at least AT the resolution…"We have changed this typo. 2.Introduction paragraph four (page 4), first sentence. Statement "which is involved in embryonic development" is too vague. Please state, briefly, the function of DACH.We have added an introduction description of DACHs known function and reference to its Drosophila homolog. 3.Introduction paragraph four (page 4). When first introducing Dc2, please define it as a conserved, functional element at DACH (i.e., since the Dc nomenclature was not used previously in the text).We have made this change. 4.Introduction paragraph four (page 4). Please provide a reference for the statement "known degeneracy of the sequences recognized by transcription factors".We have added a reference. 5.Results paragraph one (page 5), first sentence. Please restate the locus (DACH) at which Dc2 resides.We have made this change. 6.Results "Refinement of the Minimal Necessary Dc2 Enhancer". Authors state that the 424 bp fragment drives expression pattern in transgenics that is "indistingu...

show abstract

“…For example, the planarian eyes require neither Pax6 activity nor Six3 . While dachshund is critical for invertebrate eye formation (Mardon et al, 1994), it does not seem to have an important role in vertebrate eye formation (Davis et al, 2001). And last, but not least, vertebrate eye formation is Rx dependent while invertebrate eye development is Rx independent (Davis et al, 2003).…”

Section: Implications For Eye Development and Evolutionmentioning

confidence: 99%

Regulation of vertebrate eye development by Rx genes

Bailey

El‐Hodiri²,

Zhang³

et al. 2004

Int. J. Dev. Biol.

156

127

View full text Add to dashboard Cite

The paired-like homeobox-containing gene Rx has a critical role in the eye development of several vertebrate species including Xenopus, mouse, chicken, medaka, zebrafish and human. Rx is initially expressed in the anterior neural region of developing embryos, and later in the retina and ventral hypothalamus. Abnormal regulation or function of Rx results in severe abnormalities of eye formation. Overexpression of Rx in Xenopus and zebrafish embryos leads to overproliferation of retinal cells. A targeted elimination of Rx in mice results in a lack of eye formation. Mutations in Rx genes are the cause of the mouse mutation eyeless (ey1), the medaka temperature sensitive mutation eyeless (el) and the zebrafish mutation chokh. In humans, mutations in Rx lead to anophthalmia. All of these studies indicate that Rx genes are key factors in vertebrate eye formation. Because these results cannot be easily reconciled with the most popular dogmas of the field, we offer our interpretation of eye development and evolution.

show abstract

Dach1 Mutant Mice Bear No Gross Abnormalities in Eye, Limb, and Brain Development and Exhibit Postnatal Lethality

Cited by 96 publications

References 42 publications

Targeted disruption of mouse Dach1 results in postnatal lethality

Targeted disruption of mouse Dach1 results in postnatal lethality

In vivo characterization of a vertebrate ultraconserved enhancer

Regulation of vertebrate eye development by Rx genes

Contact Info

Product

Resources

About