scholarly journals ENU Mouse Mutagenesis: Generation of Mouse Mutants with Aberrant Plasma IgE Levels

2001 ◽  
Vol 124 (1-3) ◽  
pp. 25-28 ◽  
Author(s):  
Francesca Alessandrini ◽  
Thilo Jakob ◽  
Alexander Wolf ◽  
Eckhard Wolf ◽  
Rudolf Balling ◽  
...  
Keyword(s):  
Mouse Mutants ◽  
Mouse Mutagenesis

Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects

2008 ◽  
Vol 294 (2) ◽  
pp. E232-E240 ◽  
Author(s):  
Bernhard Aigner ◽  
Birgit Rathkolb ◽  
Nadja Herbach ◽  
Martin Hrabé de Angelis ◽  
Rüdiger Wanke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Large Scale ◽  
Experimental Models ◽  
Targeted Mutagenesis ◽  
Causative Mutation ◽  
Chromosomal Assignment ◽  
Screen Parameter ◽  
Mouse Mutants ◽  
Novel Alleles ◽  
Mouse Mutagenesis

More than 150 million people suffer from diabetes mellitus worldwide, and this number is expected to rise substantially within the next decades. Despite its high prevalence, the pathogenesis of diabetes mellitus is not completely understood. Therefore, appropriate experimental models are essential tools to gain more insight into the genetics and pathogenesis of the disease. Here, we describe the current efforts to establish novel diabetes models derived from unbiased, phenotype-driven, large-scale N-ethyl- N-nitrosourea (ENU) mouse mutagenesis projects started a decade ago using hyperglycemia as a high-throughput screen parameter. Mouse lines were established according to their hyperglycemia phenotype over several generations, thereby revealing a mutation as cause for the aberrant phenotype. Chromosomal assignment of the causative mutation and subsequent candidate gene analysis led to the detection of the mutations that resulted in novel alleles of genes already known to be involved in glucose homeostasis, like glucokinase, insulin 2, and insulin receptor. Additional ENU-induced hyperglycemia lines are under genetic analysis. Improvements in screen for diabetic animals are implemented to detect more subtle phenotypes. Moreover, diet challenge assays are being employed to uncover interactions between genetic and environmental factors in the pathogenesis of diabetes mellitus. The new mouse mutants recovered in phenotype-driven ENU mouse mutagenesis projects complement the available models generated by targeted mutagenesis of candidate genes, all together providing the large resource of models required for a systematic dissection of the pathogenesis of diabetes mellitus.

PHENOSITE: A WEB DATABASE INTEGRATING THE MOUSE PHENOTYPING PLATFORM AND THE EXPERIMENTAL PROCEDURES IN MICE

2007 ◽  
Vol 05 (06) ◽  
pp. 1173-1191 ◽  
Author(s):  
HIROSHI MASUYA ◽  
SUMI YOSHIKAWA ◽  
NAOHIKO HEIDA ◽  
TETSURO TOYODA ◽  
SHIGEHARU WAKANA ◽  
...  
Keyword(s):  
Large Scale ◽  
Chromosomal Location ◽  
Web Database ◽  
Phenotypic Data ◽  
Resource Information ◽  
Related Information ◽  
Mouse Mutants ◽  
Experimental Protocols ◽  
Using Data ◽  
Mouse Mutagenesis

Recently, a number of collaborative large-scale mouse mutagenesis programs have been launched. These programs aim for a better understanding of the roles of all individual coding genes and the biological systems in which these genes participate. In international efforts to share phenotypic data among facilities/institutes, it is desirable to integrate information obtained from different phenotypic platforms reliably. Since the definitions of specific phenotypes often depend on a tacit understanding of concepts that tends to vary among different facilities, it is necessary to define phenotypes based on the explicit evidence of assay results. We have developed a website termed PhenoSITE (Phenome Semantics Information with Terminology of Experiments: ), in which we are trying to integrate phenotype-related information using an experimental-evidence–based approach. The site's features include (1) a baseline database for our phenotyping platform; (2) an ontology associating international phenotypic definitions with experimental terminologies used in our phenotyping platform; (3) a database for standardized operation procedures of the phenotyping platform; and (4) a database for mouse mutants using data produced from the large-scale mutagenesis program at RIKEN GSC. We have developed two types of integrated viewers to enhance the accessibility to mutant resource information. One viewer depicts a matrix view of the ontology-based classification and chromosomal location of each gene; the other depicts ontology-mediated integration of experimental protocols, baseline data, and mutant information. These approaches rely entirely upon experiment-based evidence, ensuring the reliability of the integrated data from different phenotyping platforms.

scholarly journals Deficiency of the onco-miRNA cluster, miR-106b∼25, causes oligozoospermia and the cooperative action of miR-106b∼25 and miR-17∼92 is required to maintain male fertility

2020 ◽  
Vol 26 (6) ◽  
pp. 389-401
Author(s):  
Alicia Hurtado ◽  
Rogelio Palomino ◽  
Ina Georg ◽  
Miguel Lao ◽  
Francisca M Real ◽  
...  
Keyword(s):  
Male Fertility ◽  
Molecular Mechanisms ◽  
Mirna Cluster ◽  
Knock Out ◽  
Cooperative Action ◽  
Mouse Mutants ◽  
New Genes ◽  
Mirna Clusters ◽  
Testicular Histology ◽  
And Function

Abstract The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17∼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106b∼25, that is expressed in the same cells, were reported to have no effect on testis development and function. The aim of this work is to determine the role of these two miRNA clusters in spermatogenesis and male fertility. For this, we analyzed miR-106b∼25 and miR-17∼92 single and double mouse mutants and compared them to control mice. We found that miR-106b∼25 knock out testes show reduced size, oligozoospermia and altered spermatogenesis. Transcriptomic analysis showed that multiple molecular pathways are deregulated in these mutant testes. Nevertheless, mutant males conserved normal fertility even when early spermatogenesis and other functions were disrupted. In contrast, miR-17∼92+/−; miR-106b∼25−/− double mutants showed severely disrupted testicular histology and significantly reduced fertility. Our results indicate that miR-106b∼25 and miR-17∼92 ensure accurate gene expression levels in the adult testis, keeping them within the required thresholds. They play a crucial role in testis homeostasis and are required to maintain male fertility. Hence, we have identified new candidate genetic factors to be screened in the molecular diagnosis of human males with reproductive disorders. Finally, considering the well-known oncogenic nature of these two clusters and the fact that patients with reduced fertility are more prone to testicular cancer, our results might also help to elucidate the molecular mechanisms linking both pathologies.

The large-scale Munich ENU-mouse-mutagenesis screen

2000 ◽  
Vol 11 (7) ◽  
pp. 507-510 ◽  
Author(s):  
Dian Soewarto ◽  
Christiane Fella ◽  
Andreas Teubner ◽  
Birgit Rathkolb ◽  
Walter Pargent ◽  
...  
Keyword(s):  
Large Scale ◽  
Mutagenesis Screen ◽  
Mouse Mutagenesis

scholarly journals PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3609-3617 ◽  
Author(s):  
Jinjun Dang ◽  
Lei Wei ◽  
Jeroen de Ridder ◽  
Xiaoping Su ◽  
Alistair G. Rust ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Suppressor ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
Human Leukemia ◽  
Key Points ◽  
Leukemia Development ◽  
Common Target ◽  
Mouse Mutagenesis

Key Points Heterozygous alterations of Pax5, the most common target of genetic alteration in ALL, promote ALL in mouse mutagenesis models. Leukemia development is accompanied by the acquisition of genetic alterations commonly observed in human leukemia.

Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4361-4371 ◽  
Author(s):  
H. Toresson ◽  
S.S. Potter ◽  
K. Campbell
Keyword(s):  
Cerebral Cortex ◽  
Gene Function ◽  
Abnormal Development ◽  
Loss Of Function ◽  
Embryonic Mouse ◽  
Molecular Identity ◽  
Mouse Mutants ◽  
Germinal Zone ◽  
Genetic Mechanisms ◽  
Dlx Genes

We have examined the genetic mechanisms that regulate dorsal-ventral identity in the embryonic mouse telencephalon and, in particular, the specification of progenitors in the cerebral cortex and striatum. The respective roles of Pax6 and Gsh2 in cortical and striatal development were studied in single and double loss-of-function mouse mutants. Gsh2 gene function was found to be essential to maintain the molecular identity of early striatal progenitors and in its absence the ventral telencephalic regulatory genes Mash1 and Dlx are lost from most of the striatal germinal zone. In their place, the dorsal regulators, Pax6, neurogenin 1 and neurogenin 2 are found ectopically. Conversely, Pax6 is required to maintain the correct molecular identity of cortical progenitors. In its absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and Dlx genes are found ectopically. These reciprocal alterations in cortical and striatal progenitor specification lead to the abnormal development of the cortex and striatum observed in Pax6 (small eye) and Gsh2 mutants, respectively. In support of this, double homozygous mutants for Pax6 and Gsh2 exhibit significant improvements in both cortical and striatal development compared with their respective single mutants. Taken together, these results demonstrate that Pax6 and Gsh2 govern cortical and striatal development by regulating genetically opposing programs that control the expression of each other as well as the regionally expressed developmental regulators Mash1, the neurogenins and Dlx genes in telencephalic progenitors.

scholarly journals Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency

2018 ◽  
Vol 215 (5) ◽  
pp. 1327-1336 ◽  
Author(s):  
Baerbel Keller ◽  
Moneef Shoukier ◽  
Kathrin Schulz ◽  
Arshiya Bhatt ◽  
Ines Heine ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
X Chromosome ◽  
Immune Cell ◽  
Antibody Deficiency ◽  
Limited Information ◽  
Cell Type ◽  
Interacting Protein ◽  
Mouse Mutants ◽  
Cell Type Specific

Ubiquitously expressed Cbl-interacting protein of 85 kD (CIN85) is a multifunctional adapter molecule supposed to regulate numerous cellular processes that are critical for housekeeping as well as cell type–specific functions. However, limited information exists about the in vivo roles of CIN85, because only conditional mouse mutants with cell type–specific ablation of distinct CIN85 isoforms in brain and B lymphocytes have been generated so far. No information is available about the roles of CIN85 in humans. Here, we report on primary antibody deficiency in patients harboring a germline deletion within the CIN85 gene on the X chromosome. In the absence of CIN85, all immune cell compartments developed normally, but B lymphocytes showed intrinsic defects in distinct effector pathways of the B cell antigen receptor, most notably NF-κB activation and up-regulation of CD86 expression on the cell surface. These results reveal nonredundant functions of CIN85 for humoral immune responses.

Use of the UCHT1 monoclonal antibody to explore mouse mutants and development

Nature ◽  
1982 ◽  
Vol 300 (5891) ◽  
pp. 441-443 ◽  
Author(s):  
K. W. T. Caddy ◽  
D. L. Patterson ◽  
T. J. Biscoe
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Mutants

Development of Structures and Transport Functions in the Mouse Placenta

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 180-193 ◽  
Author(s):  
Erica D. Watson ◽  
James C. Cross
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cell Biology ◽  
Fetal Death ◽  
Nutrient Transport ◽  
Growth Restriction ◽  
Molecular Pathways ◽  
Placental Development ◽  
Mouse Mutants ◽  
Mouse Placenta

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.

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