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Homozygous Embryos (homozygous + embryo)
Selected AbstractsMan1, an inner nuclear membrane protein, regulates left,right axis formation by controlling nodal signaling in a node-independent mannerDEVELOPMENTAL DYNAMICS, Issue 12 2008Akihiko Ishimura Abstract Man1, an inner nuclear membrane protein, regulates transforming growth factor , signaling by interacting with receptor-associated Smads. In Man1 -deficient (Man1,/,) embryos, vascular remodeling is perturbed by misregulation of Smad activity. Here, we show that Man1,/, embryos exhibit abnormal heart morphogenesis including the looping abnormality. We searched for the molecular basis underlying the heart abnormalities and found that the left side-specific genes responsible for left,right (LR) asymmetry, Nodal, Lefty2, and Pitx2, were expressed bilaterally in the lateral plate mesoderm and that their expression was enhanced significantly in mutants. Notably, Lefty1, a marker for the midline barrier, was maintained in Man1,/, mutants. Crossing Man1,/+ with Nodal hypomorphs (Nodalneo/+), in which Nodal signaling in the node is disrupted, to generate double homozygous embryos (Man1,/,; Nodalneo/neo) revealed that the bilateral Nodal was retained in Man1,/,; Nodalneo/neo embryos. These results suggest that Man1 regulates LR asymmetry by controlling Nodal signaling in a node-independent manner. Developmental Dynamics 237:3565,3576, 2008. © 2008 Wiley-Liss, Inc. [source] Characterization of teleost Mdga1 using a gene-trap approach in medaka (Oryzias latipes)GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 8 2009Shinya Sano Abstract MAM domain containing glycosilphosphatidilinositol anchor 1 (MDGA1) is an IgCAM protein present in many vertebrate species including humans. In mammals, MDGA1 is expressed by a subset of neurons in the developing brain and thought to function in neural cell migration. We identified a fish ortholog of mdga1 by a gene-trap screen utilizing the Frog Prince transposon in medaka (Japanese killifish, Oryzias latipes). The gene-trap vector was inserted into an intronic region of mdga1 to form a chimeric protein with green fluorescent protein, allowing us to monitor mdga1 expression in vivo. Expression of medaka mdga1 was seen in various types of embryonic brain neurons, and specifically in neurons migrating toward their target sites, supporting the proposed function of MDGA1. We also isolated the closely related mdga2 gene, whose expression partially overlapped with that of mdga1. Despite the fact that the gene-trap event eliminated most of the functional domains of the Mdga1 protein, homozygous embryos developed normally without any morphological abnormality, suggesting a functional redundancy of Mdga1 with other related proteins. High sequential homology of MDGA proteins between medaka and other vertebrate species suggests an essential role of the MDGA gene family in brain development among the vertebrate phylum. genesis 47:505,513, 2009. © 2009 Wiley-Liss, Inc. [source] High-resolution mapping of the Gli3 deletion in the mouse extra-toesH mutantGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 3 2007Matthieu Genestine Abstract Extra-toes is a semidominant mutation that affects the Gli3 gene and provokes limb and brain abnormalities. Among the different alleles of this mutation, XtH is due to a deletion that has not yet been fully characterized. Using a PCR-based strategy, we undertook a high-resolution mapping of this deletion and confirmed that XtH is a null allele of Gli3. We further designed a PCR test to identify unequivocally heterozygous and homozygous embryos from their wild-type littermates. Despite the length of the XtH deletion, available data on the mouse genome indicate that no genes other than Gli3 are deleted in XtH mutants. Thus, the XtH mutation can be used as a model for studying the effects that absence of Gli3 function has during development. genesis 45:107,112, 2007. © 2007 Wiley-Liss, Inc. [source] A gene trap knockout of the abundant sperm tail protein, outer dense fiber 2, results in preimplantation lethality,GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 11 2006Nicholas A. Salmon Abstract Outer dense fiber 2 (Odf2) is highly expressed in the testis where it encodes a major component of the outer dense fibers of the sperm flagellum. Furthermore, ODF2 protein has recently been identified as a widespread centrosomal protein. While the expression of Odf2 highlighted a potential role for this gene in male germ cell development and centrosome function, the in vivo function of Odf2 was not known. We have generated Odf2 knockout mice using an Odf2 gene trapped embryonic stem cell (ESC) line. Insertion of a gene trap vector into exon 9 resulted in a gene that encodes a severely truncated protein lacking a large portion of its predicted coil forming domains as well as both leucine zipper motifs that are required for protein,protein interactions with ODF1, another major component of the outer dense fibers. Although wild-type and heterozygous mice were recovered, no mice homozygous for the Odf2 gene trap insertion were recovered in an extended breeding program. Furthermore, no homozygous embryos were found at the blastocyst stage of embryonic development, implying a critical pre-implantation role for Odf2. We show that Odf2 is expressed widely in adults and is also expressed in the blastocyst stage of preimplantation development. These findings are in contrast with early studies reporting Odf2 expression as testis specific and suggest that embryonic Odf2 expression plays a critical role during preimplantation development in mice. genesis 44:515,522, 2006. Published 2006 Wiley-Liss, Inc. [source] Truncation of the MLL gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryosGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 4 2001Paul Ayton Abstract Summary: The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives. genesis 30:201,212, 2001. © 2001 Wiley-Liss, Inc. [source] | ||||||||||