hNGFR100W/wt
| Status | Under development - register interest |
| EMMA ID | EM:15775 |
| Citation information | RRID:IMSR_EM:15775 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 | hNGFR100W/wt |
| Alternative name | hNGFR100W/wt |
| Strain type | Targeted Mutant Strains : Knock-in |
| Allele/Transgene symbol | Ngftm1(NGF*)Cat |
| Gene/Transgene symbol | Ngf |
Information from provider
| Provider | Simona Capsoni |
| Provider affiliation | University of Ferrara |
| Genetic information | The R100W mutation in human nerve growth factor (NGF) causes Hereditary Sensory and Autonomic Neuropathy type V. We generated mutant mice harboring the 661-C to T mutation in the human NGF gene at the mouse Ngf locus (this strain: hNGFR100W/wt, EMMA strain EM:15575). We also generated mutant mice harboring the human NGF wild-type gene at the mouse Ngf locus (EMMA strain EM:15574) to control for this strain (hNGFR100W/wt). 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 NGFR100W/R100W mice die by P30. In addition, the density of cholinergic neurons of homozygous mice is unaffected in the medial septum and in the nucleus basalis of Meynert, whereas it is increased specifically in the striatum.Heterozygous:Heterozygous mice thrive normally and show no visible gross deficit. The phenotype of heterozygous NGFR100W/wt mice has been analyzed in detail, during youth (2 months) and adulthood (6 months). Chemical nociception induced by capsaicin injection in the hindpaw is impaired at both ages. Thermal nociception is normal at 2 months of age but decreases at 6 months, with adult NGFR100W/wt mice displaying a higher latency to respond to a high-temperature stimulus. Cold sensitivity is reduced at both ages. In NGFR100W/wt mice, a non-noxious stimulus represented by a small piece of tape applied to the hairy skin takes more time to induce a removal reaction only at 6 months of age. The response to gentle stroking of the glabrous skin is normal at both time points. DRG neurons of NGFR100W/wt mice are morphologically normal, with no alteration in the different DRG subpopulations, whereas skin innervation is reduced. Cognition tested in object recognition and Y maze is normal. |
| Breeding history | pCMV6-XL5-human NGFR100W was generated using site-specific mutagenesis PCR. The targeting constructs were generated using classical cloning technologies. Briefly, a BAC (bacterial artificial chromosome; clone RP24-160F12) containing the entire regions of interest flanking the NGF sequence, was used to generate intermediate plasmids by cloning in pBluescript SK(-) the 5′ homology arm (from 89489 to 94076, restriction site MfeI) and 3′ homology arm (from 94803 to 99710, restriction site HindIII). The human NGFR100W coding sequence was cloned in the pKO2.1 targeting vector carrying the DTA (diptheria toxin A) negative selection cassette. The targeting vector was transfected into R1-p.15 cells (129/Sv background) and positive clones were selected using neomycin resistance and injected into C57BL/6 blastocysts. A “cre-deleter” strain (B6.C-Tg(CMV-cre)1Cgn/J; The Jackson Lab. stock n. 006054), expressing the cre recombinase under the cytomegalovirus (CMV) promoter was used 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 |
Literature references
- Cholinergic striatal neurons are increased in HSAN V homozygous mice despite reduced NGF bioavailability.;Testa Giovanna, Calvello Mariantonietta, Cattaneo Antonino, Capsoni Simona, ;2019;Biochemical and biophysical research communications;509;763-766; 30612733
- The NGFR100W Mutation Specifically Impairs Nociception without Affecting Cognitive Performance in a Mouse Model of Hereditary Sensory and Autonomic Neuropathy Type V.;Testa Giovanna, Mainardi Marco, Morelli Chiara, Olimpico Francesco, Pancrazi Laura, Petrella Carla, Severini Cinzia, Florio Rita, Malerba Francesca, Stefanov Antonia, Strettoi Enrica, Brandi Rossella, Arisi Ivan, Heppenstall Paul, Costa Mario, Capsoni Simona, Cattaneo Antonino, ;2019;The Journal of neuroscience : the official journal of the Society for Neuroscience;39;9702-9715; 31685654