| 1. |
- Ching, Yung-Hao, et al.
(författare)
-
High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5
- 2010
-
Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 11, s. 106-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a similar to 50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals. Results: We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis. Conclusion: This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.
|
|
| 2. |
- Ishiguro, K, et al.
(författare)
-
Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes
- 2014
-
Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 28:6, s. 594-607
-
Tidskriftsartikel (refereegranskat)abstract
- During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic chromosome movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue in chromosome biology. Here, we show that homolog recognition or association initiates upon entry into meiotic prophase before axis assembly and double-strand break (DSB) formation. This homolog association develops into tight pairing only during or after axis formation. Intriguingly, the ability to recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere-directed chromosome movement is abolished, and this is the case even in Spo11 knockout spermatocytes, in which DSB-dependent DNA homology search is absent. Disruption of meiosis-specific cohesin RAD21L precludes the initial association of homologs as well as the subsequent pairing in spermatocytes. These findings suggest the intriguing possibility that homolog recognition is achieved primarily by searching for homology in the chromosome architecture as defined by meiosis-specific cohesin rather than in the DNA sequence itself.
|
|
| 3. |
- Kumar, R, et al.
(författare)
-
MEI4 – a central player in the regulation of meiotic DNA double-strand break formation in the mouse
- 2015
-
Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 128:9, s. 1800-1811
-
Tidskriftsartikel (refereegranskat)abstract
- The formation of programmed DNA double strand breaks (DSBs) at the beginning of meiotic prophase marks the initiation of meiotic recombination. Meiotic DSBs are catalyzed by SPO11 and their repair takes place on meiotic chromosome axes. The evolutionarily conserved MEI4 protein is required for meiotic DSB formation and is localized on chromosome axes. Here we show that HORMAD1, one of the meiotic chromosome axis components, is required for MEI4 localization. Importantly, the quantitative correlation between the level of axis-associated MEI4 and DSB formation suggests that axis-associated MEI4 could be a limiting factor for DSB formation. We also show that MEI1, REC8 and RAD21L are important for proper MEI4 localization. These findings on MEI4 dynamics during meiotic prophase suggest that the association of MEI4 to chromosome axes is required for DSB formation, and that the loss of this association upon DSB repair could contribute to turning off meiotic DSB formation.
|
|
