IMPC phenotypes (gene matching)
hTRKAR649W/m
| Status | Under development - register interest |
| EMMA ID | EM:15776 |
| Citation information | RRID:IMSR_EM:15776 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | hTRKAR649W/m |
| Alternative name | hTRKAR649W/m |
| Strain type | Targeted Mutant Strains : Knock-in |
| Allele/Transgene symbol | Ntrk1hTRKAR649W/m |
| Gene/Transgene symbol | Ntrk1 |
Information from provider
| Provider | Simona Capsoni |
| Provider affiliation | University of Ferrara |
| Genetic information | The R649W mutation in the human NTRK1 gene causes Hereditary Sensory and Autonomic Neuropathy type IV. We generated knock-in mice harboring the R649W mutation in the human NTRK1 gene at the mouse Ntrk1 locus (this strain: hTRKAR649W/m, EM:15776). We also generated mutant mice harboring the human NTRK1 wild-type gene at the mouse Ntrk1 locus (EMMA strain EM:15577) to control for this strain (hTRKAR649W/m). We cannot guarantee the genotype and the recipient will have to take the responsibility to carry out all the necessary genotypic checks (including sequencing of the PCR products to distinguish wild-type from mutant animals). |
| Phenotypic information | Homozygous:Homozygous NTRK1R649W/m mice die by P30Heterozygous:TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. |
| Breeding history | To generate the human TrkAR649W/m mouse line, the starting point was the targeting vector AMB1- Tg-pA, containing the coding sequence of the human NTRK1 (TRKA). We performed a site-specific mutagenesis PCR to introduce the HSAN IV R649W mutation in the targeting vector AMB1-Tg-pA containing the coding sequence of the human NTRK1. The mutated AflII-FseI segment from the AMB-Tg-pA vector replaced the AflII-FseI DNA segment of the vector AMB1-HR containing the human NTRK1 cDNA, long and short homology regions and the positive selection neomycin gene flanked by LoxP sites. The final targeting vector AMB1-HR carrying the R649W mutation in the humanized NTRK1, was linearized prior to electroporation, then transfected into R1-p.15 cells (129/Sv background) and positive clones were selected using neomycin resistance. Then, positive clones were injected into blastocysts from C57BL/6 mice and chimeric animals were crossed with “cre-deleter” mice (B6.C-Tg(CMV-cre)1Cgn/J; The Jackson Lab. stock n. 006054), expressing the cre recombinase under the cytomegalovirus (CMV) promoter to remove the neomycin selection cassette. |
| References |
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| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | CNR, Consiglio Nazionale delle Ricerche, Monterotondo, Italy |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Hereditary sensory and autonomic neuropathy type 4 / Orphanet_642
- Familial medullary thyroid carcinoma / Orphanet_99361
MGI phenotypes (gene matching)
- mottled coat / MGI
- ulcerated paws / MGI
- small dorsal root ganglion / MGI
- decreased sensory neuron number / MGI
- abnormal sensory neuron innervation pattern / MGI
- abnormal sympathetic ganglion morphology / MGI
- small superior cervical ganglion / MGI
- abnormal cholinergic neuron morphology / MGI
- small trigeminal ganglion / MGI
- skin lesions / MGI
- decreased body size / MGI
- corneal opacity / MGI
- blepharoptosis / MGI
- abnormal vibrissae reflex / MGI
- unresponsive to tactile stimuli / MGI
- abnormal pain threshold / MGI
- increased thermal nociceptive threshold / MGI
- miotic pupils / MGI
- premature death / MGI
- abnormal digit morphology / MGI
- no abnormal phenotype detected / MGI
- abnormal chemical nociception / MGI
- abnormal nociception after inflammation / MGI
- no phenotypic analysis / MGI
- nervous system phenotype / MGI
- abnormal thermosensation / MGI
- decreased thermal nociceptive threshold / MGI
- abnormal sympathetic nervous system physiology / MGI
- abnormal proprioceptive neuron morphology / MGI
- abnormal neuron physiology / MGI
- hearing/vestibular/ear phenotype / MGI
- behavior/neurological phenotype / MGI
- abnormal neurite morphology / MGI
- increased muscle spindle number / MGI
- abnormal sensory neuron physiology / MGI
- mortality/aging / MGI
- postnatal lethality, incomplete penetrance / MGI
Literature references
- Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.;Pacifico Paola, Testa Giovanna, Amodeo Rosy, Mainardi Marco, Tiberi Alexia, Convertino Domenica, Arevalo Juan Carlos, Marchetti Laura, Costa Mario, Cattaneo Antonino, Capsoni Simona, ;2023;Human molecular genetics;32;1380-1400; 36537577