Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation and standardized, systemic phenotypic analysis of Kctd1 mutant mice

ABSTRACT: Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically mutant line HST014 was established and further analyzed. The causative mutation was detected in the gene Kctd1 which leads to the amino acid exchange Kctd1I27N thereby affecting the functional BTB domain of the protein. This line is the first mouse model harbouring a Kctd1 mutation. Kctd1I27N homozygous mutant mice die perinatally. Standardized, systemic phenotypic analysis of heterozygous mutants was carried out in the German Mouse Clinic. Systematic morphological investigation of the external physical appearance found no mutation-specific differences. Main phenotypic changes were kidney dysfunction, minor cardiovascular and neurological alterations as well as low plasma corticosterone levels. Genome-wide RNA expression analysis at the age of 4 months revealed few regulated genes in brain and heart, and over 100 significantly regulated genes in kidneys of heterozygous mutants.

ORGANISM(S): Mus musculus

PROVIDER: GSE47005 | GEO | 2014/05/02

SECONDARY ACCESSION(S): PRJNA203265

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Generation and standardized, systemic phenotypic analysis of Kctd1 mutant mice

Project description:Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically mutant line HST014 was established and further analyzed. The causative mutation was detected in the gene Kctd1 which leads to the amino acid exchange Kctd1I27N thereby affecting the functional BTB domain of the protein. This line is the first mouse model harbouring a Kctd1 mutation. Kctd1I27N homozygous mutant mice die perinatally. Standardized, systemic phenotypic analysis of heterozygous mutants was carried out in the German Mouse Clinic. Systematic morphological investigation of the external physical appearance found no mutation-specific differences. Main phenotypic changes were kidney dysfunction, minor cardiovascular and neurological alterations as well as low plasma corticosterone levels. Genome-wide RNA expression analysis at the age of 4 months revealed few regulated genes in brain and heart, and over 100 significantly regulated genes in kidneys of heterozygous mutants. Total RNA obtained from 4 mutant and 5 wild type control mice

2014-05-02 | E-GEOD-47005 | biostudies-arrayexpress

A recessive point mutation is responsible for pleiotropic effects in a scube3 mutant mouse

Project description:We established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.

2017-02-10 | GSE56402 | GEO

Jag1K295*/+ as a mouse model for Alagille syndrome

Project description:A new mouse mutant was identified at the Munich ENU mutagenesis project due to hyperactivity, head tossing, and circling behaviour. Neurological and gross morphological phenotyping of these mutant mice revealed impairment of the vestibular system. Using whole genome exome sequencing and a custom-made variant calling pipeline, we identified the causative mutation as an A->T substitution on the chromosome 2 at the position 128 in the exon 6 of jagged 1 (Jag1) gene. This introduces a premature termination codon at the position 883 of the cDNA. In humans, mutations in the JAG1 gene are associated with Alagille syndrome (ALGS1 ), a multisystem developmental disorder mainly affecting small bile ducts in the liver, but also heart, skeleton, and eyes, and occasionally also kidney or inner ears. Further examination of the Jag1K295*/+ mutant mouse line disclosed multiorgan deficiencies, such as cardiac liver congestion, bile duct hypoplasia, mild nephropathy, subvalvular hypertrophy of the right ventricle, and mild growth retardation. No skeletal abnormalities could be detected. In summary, we report a novel mouse model for Alagille syndrome, Jag1K295*/+, which resembles most of the features of the mild form of Alagille syndrome observed in patients. Total RNA obtained from liver of 4 male heterozygous Jag1K295*/+ and 4 male wildtype mice

2014-10-01 | E-GEOD-55602 | biostudies-arrayexpress

Jag1K295*/+ as a mouse model for Alagille syndrome

2014-10-01 | GSE55602 | GEO

Project description:Dnaaf1 and Lrrc48 ENU mutants

| PRJNA325945 | ENA

Mouse kidney glomeruli. Control vs. podocin(R231Q/A268V)

Project description:Similar to human patients, mice with the compound heterozygous mutation podocin R231Q/A268V, develop a late onset FSGS. Here, we did a proteomics anaylsis of kidney glomeruli before the onset of disease (mice at 3 weeks of age). Analysis of the data reveals that there are no developmental changes in the proteome of compund heterozygous mice.

2020-05-15 | PXD018326 | Pride

A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation. [human]

Project description:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 100-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation.

2017-10-18 | GSE69396 | GEO

A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation. [mouse]

2017-10-18 | GSE69390 | GEO

ENU derived mouse line AEA001: A model for osteoporosis carrying a mutation in Ednra

Project description:Transcriptome analysis of white adipose tissue and bone (femur of the hind limbs) of the AEA001 mutant mouse. ENU generated mouse lines for osteoporosis. The mutation in the Ednra gene causes big ears and a flat short head. Due to a decreased body mass and a trend towards decreased glucose level white adipose tissue was analysed.

2014-09-01 | GSE40428 | GEO

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional disruptions

Project description:Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNMT3A, a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a DNMT3A P900L/+ mouse mimicking a mutation with mild-to-moderate severity, and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identify mutation-specific dysregulated genes which may contribute to variable disease severity. Shared transcriptomic disruption identified across mutations overlaps dysregulation observed in other developmental disorder models and likely drives common phenotypes. Together, our findings define central drivers of DNMT3A disorders and illustrate how variable epigenomic disruption contributes to phenotypic heterogeneity in neurodevelopmental disease.

2023-11-08 | GSE225372 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data