Animal Models

Animal models represent an important tool for translating scientific discoveries in the laboratory to developing medicines for patients at the bedside.  As part of its commitment to providing research tools to help NF1 investigators, NTAP has dedicated itself to the development, use, and publicity of high quality animal models.  Listed below are animal models currently available to the NF1 research community at large, some of which have been used, or developed, in NTAP funded projects.  NTAP is happy to provide information or help facilitate discussions about these models, to help drive your research.

MOUSE MODELS

DhhCre-Nf1fl/fl     
Uses:  Genetically engineered model for evaluating therapeutics and gene expression analysis.  Used in NTAP funded projects, including as a key model as part of the NFTC collaboration.
Source: Nancy Ratner, Ph.D.

Krox20;Nf1flox/−
Uses: Genetically engineered model for evaluating therapeutics, dosing schedules, and investigating patterns of resistance.  Used in NTAP funded projects, including as a key model as part of the NFTC collaboration.
Source: D. Wade Clapp, M.D.

Transgenic Nf1 Nf1+/-; p53+/-  
Uses: Genetically engineered model for evaluating safety, biomarkers, and therapeutics. Dr. Verena Staedtke (one of NTAP’s Francis Collins Scholars) used this model as part of her project evaluating Clostridium Novi for MPNST
Source: Karen Cichowski, Ph.D., Tyler Jacks, Ph.D.

Nestin-CreER+; Nf1fl/fl or flox/+
Uses: Genetically engineered model for evaluating MEK-inhibitor based treatment strategies.  Dr. Miriam Bornhorst (one of NTAP’s Francis Collins Scholars) used this model in her project probing the timing of critical events preceding onset of OPG.
Source: Yuan Zhu, Ph.D.

Nf1-/- ;R26R-LacZ-Luciferase DNSC
Uses: Genetically engineered model at the level of cell of origin for testing of therapeutics. Used and further optimized in an NTAP funded project to evaluate different therapeutics and explore the possibility of long term storage of DNSCs.
Source: Lu Le, M.D., Ph.D. (Lu.Le@UTSouthwestern.edu)

Prss56-positive BC cells
Uses: Genetically engineered model for the identification and characterization of the cell type(s), among the BC derivatives in the skin, and testing of therapeutics.  Used in an NTAP funded project as part of the cNF initiative.
Source: Piotr Topilko, Ph.D 

Nonsense mutation (c.2041C>T; p.Arg681*) and Missense mutation (c.2542G>C; p.Gly848Arg)
Uses: Mutation specific model for testing of therapeutics.
Source: Robert Kesterson, Ph.D

CAD5-CreERT2/Rosa26-LSL-td-Tomato/Nf1flox/flox
Uses: Model for probing molecular regulation of endothelial cells by NF1
Source:  Kevin Pumiglia, Ph.D

Col2α1-Cre/Nf1flox/flox
Uses: Model to assess Nf1 loss of function in chondrocytes, and skeletal manifestations
Source: Florent Elefteriou, PhD

PeriCre+;Nf1flox/−, and Col2.3Cre+;Nf1flox/−
Uses: Model to assess osseous manifestations of NF1
Source: Feng-Chun Yang, M.D, Ph.D

Mx1-Cre; Nf1flox/flox
Uses: Preclinical Mouse Model of JMML
Source: Kevin Shannon, M.D

Synapsin 1-Cre; Nf1flox/flox ; Nf1+/-; p53+/- cis
Uses: Mouse model of conditional knockout of Nf1 in neurons
Source: Luis Parada, Ph.D

PORCINE MODELS

Yucatan miniswine with Exon 42 deletion (NF1+/ex42del)
Uses: Genetically engineered large animal model of NF1 (produced via recombinant adeno-assisted virus mediated gene targeting and somatic cell nuclear transfer), that recapitulates molecular and phenotypic hallmarks of the human disease, for studying biology of NF type 1 disease pathogenesis and testing of therapeutics.
Source: Jill Weimer, Ph.D

Ossabaw miniswine with R1947 mutation (NF1+/R1947*)
Uses: Genetically engineered large animal model of NF1 (produced via gene editing by TALEN), that recapitulates molecular and phenotypic hallmarks of the human disease, for studying biology of NF type 1 disease pathogenesis and testing of therapeutics.
Source: David Lagerspaeda, Ph.D

ZEBRAFISH MODELS

nf1a+/−; nf1b−/−; p53e7/e7
Uses: Model of NF1 that recapitulates molecular and phenotypic hallmarks of the human disease.
Source: Thomas Look, M.D.

DROSOPHILA MODELS

DFakCG1 null mutation
Uses: Model for probing control of peripheral nerves
Source: Michael Stern, Ph.D