|Institutional Source||Beutler Lab|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R0062 (G1)|
|Chromosomal Location||88971790-89131013 bp(+) (GRCm38)|
|Type of Mutation||critical splice donor site (2 bp from exon)|
|DNA Base Change (assembly)||T to C at 89010966 bp|
|Amino Acid Change|
|Ref Sequence||ENSEMBL: ENSMUSP00000023828 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000023828]|
|Predicted Effect||probably null
|Meta Mutation Damage Score||0.544|
|Coding Region Coverage||
|Validation Efficiency||91% (72/79)|
|MGI Phenotype||Strain: 2674124
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for an insertional mutation exhibit embryonic lethality and neurulation defects resulting in the arrest of gastrulation movements and abnormal left-right specification in the heart. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Rttn||
|Protein Function and Prediction|
Rttn encodes rotatin, a novel transmembrane protein that is required for axial rotation, left-right specification, and notochord development in embryos (1). Additional studies indicate that rotatin is required for the maintenance of normal ciliary structure (2).
Rttn is expressed from embryonic day (E) 7.5 through embryonic development (1). At E8.5, Rttn is expressed in the telencephalon, mesoderm, somites, and notochord (1). At E9.5, Rttn expression persists in the somites with expression extending to the forelimb bud, basal forebrain, and first branchial arch (1). At E11.5 and E12.5, Rttn expression was detected in the heart primordium and the expression in the branchial arches was increased (1). The Rttn protein colocalizes with basal bodes at the primary cilium in human fibroblasts (2). In the embryonic mouse brain, rotatin localized to the marginal zone of the developing mouse cortex and in the upper cortical layers (2).
Mutations in RTTN are linked to polymicrogyria with seizures [OMIM: 614833; (2)]. Patients with this disorder had microcephaly, moderate to severe mental retardation, poor speech, dysarthria, and seizures (2).
RttnGt(pGT1.8geo)7Pgr/ Gt(pGT1.8geo)7Pgr; MGI:2674124
involves: 129S1/Sv * 129X1/SvJ * NMRI
Homozygotes with this gene-trapped allele exhibit embryonic lethality during organogenesis (E9.5-E11.5), randomized heart looping, pericardial effusion, abnormal axial rotation, abnormal somite development, abnormal neural tube morphology/development, and decreased embryo size (1).
1. Faisst, A. M., Alvarez-Bolado, G., Treichel, D., and Gruss, P. (2002) Rotatin is a Novel Gene Required for Axial Rotation and Left-Right Specification in Mouse Embryos. Mech Dev. 113, 15-28.
2. Kheradmand Kia, S., Verbeek, E., Engelen, E., Schot, R., Poot, R. A., de Coo, I. F., Lequin, M. H., Poulton, C. J., Pourfarzad, F., Grosveld, F. G., Brehm, A., de Wit, M. C., Oegema, R., Dobyns, W. B., Verheijen, F. W., and Mancini, G. M. (2012) RTTN Mutations Link Primary Cilia Function to Organization of the Human Cerebral Cortex. Am J Hum Genet. 91, 533-540.
|Science Writer||Anne Murray|