|Institutional Source||Beutler Lab|
|Gene Name||SLIT and NTRK-like family, member 5|
|Is this an essential gene?||Possibly essential (E-score: 0.508)|
|Stock #||P0019 (G1)|
|Chromosomal Location||111675097-111683141 bp(+) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||A to G at 111680594 bp|
|Amino Acid Change||Aspartic acid to Glycine at position 550 (D550G)|
|Ref Sequence||ENSEMBL: ENSMUSP00000041499 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000042767] [ENSMUST00000227891]|
|Predicted Effect||possibly damaging
AA Change: D550G
PolyPhen 2 Score 0.879 (Sensitivity: 0.82; Specificity: 0.94)
AA Change: D550G
|Predicted Effect||probably benign
|Meta Mutation Damage Score||0.1979|
|Coding Region Coverage||
|Validation Efficiency||63% (57/90)|
|MGI Phenotype||Strain: 4459459
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Members of the SLITRK family, such as SLITRK5, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, including SLITRK5, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003 [PubMed 14557068]).[supplied by OMIM, Mar 2008]
PHENOTYPE: Mice homozygous for a null allele have abnormal medium spiny neuron morphology and exhibit behavioral abnormalities. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Slitrk5||
|Protein Function and Prediction|
Slitrk5 is a single-pass transmembrane protein and member of the Slitrk family; the proteins contain two extracellular leucine-rich repeat domains similar to Slit proteins, and a carboxy-terminal domain similar to Trk neurotrophin receptors (1). Overexpression of Slitrk5 suppressed neurite outgrowth in neuroblastoma cells (2).
Slitrk5 is predominately expressed in neural tissues, with highest expressed in the adult cerebral cortex (2). However, Slitrk5 is expressed in hematopoietic progenitors (3) as well as in human leukemias, embryonic stem cells and subsets of endothelial cells (4). Another study found that, by RT-PCR ELISA, SLITRK5 is highly expressed in adult amygdala (5). Intermediate expression was detected in whole adult brain, fetal brain, ovary, and all other specific brain regions examined. Weak expression was detected in lung, pancreas, and testis, and no expression was detected in heart, skeletal muscle, kidney, pancreas, spleen, and fetal liver (5). In situ hybridization of developing mouse brain detected broad Slitrk5 expression, with significant expression in the subventricular zone, cortical plate, thalamus, hypothalamus, and pyramidal cell layer of hippocampus (6). Other studies detected the Slitrk5 protein in striatal neurons as well as in dendritic spines that are positive for post-synaptic density protein-95 (PSD95) in cocultures of cortical neurons (1).
involves: 129S/Sv * C57BL/6
Mice homozygous for a null allele have abnormal medium spiny neuron morphology and exhibit behavioral abnormalities (1). Loss of a neuron-specific transmembrane protein, SLIT and NTRK-like protein-5 (Slitrk5), leads to OCD-like behaviors in mice, which manifests as excessive self-grooming and increased anxiety-like behaviors, and is alleviated by the selective serotonin reuptake inhibitor fluoxetine. Slitrk5−/− mice show selective overactivation of the orbitofrontal cortex, abnormalities in striatal anatomy and cell morphology and alterations in glutamate receptor composition, which contribute to deficient corticostriatal neurotransmission.
1. Shmelkov, S. V., Hormigo, A., Jing, D., Proenca, C. C., Bath, K. G., Milde, T., Shmelkov, E., Kushner, J. S., Baljevic, M., Dincheva, I., Murphy, A. J., Valenzuela, D. M., Gale, N. W., Yancopoulos, G. D., Ninan, I., Lee, F. S., and Rafii, S. (2010) Slitrk5 Deficiency Impairs Corticostriatal Circuitry and Leads to Obsessive-Compulsive-Like Behaviors in Mice. Nat Med. 16, 598-602, 1p following 602.
2. Aruga, J., Yokota, N., and Mikoshiba, K. (2003) Human SLITRK Family Genes: Genomic Organization and Expression Profiling in Normal Brain and Brain Tumor Tissue. Gene. 315, 87-94.
3. Shmelkov, S. V., Visser, J. W., and Belyavsky, A. V. (2001) Two-Dimensional Gene Expression Fingerprinting. Anal Biochem. 290, 26-35.
4. Milde, T., Shmelkov, S. V., Jensen, K. K., Zlotchenko, G., Petit, I., and Rafii, S. (2007) A Novel Family of Slitrk Genes is Expressed on Hematopoietic Stem Cells and Leukemias. Leukemia. 21, 824-827.
5. Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1998) Prediction of the Coding Sequences of Unidentified Human Genes. XII. the Complete Sequences of 100 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 5, 355-364.
|Science Writer||Anne Murray|