Value Proposition
· Novel genetic model for studying peripheral nervous system development - The Erbb3^I449S mutation provides a unique loss-of-function model that specifically affects nerve fasciculation and branching
· Precise developmental timing - Embryonic lethality at day 14.5 allows for detailed study of early peripheral nerve development without confounding postnatal effects
· ENU-generated point mutation - Single amino acid substitution (I449S) offers a more physiologically relevant model than complete gene knockouts
Unmet Need
ERBB3 is a critical receptor tyrosine kinase essential for peripheral nervous system development, particularly in nerve fasciculation and axon guidance. Current research relies heavily on complete Erbb3 knockout models that result in early embryonic lethality, limiting the ability to study specific developmental processes and potentially masking subtle phenotypic effects. The I449S point mutation provides a unique opportunity to study ERBB3 loss-of-function in a controlled manner, as homozygous mutants survive until E14.5, allowing detailed analysis of peripheral nerve development before lethality occurs.
Technology Description
Researchers at Johns Hopkins have developed a novel mouse strain carrying a loss of function point mutation (I449S) in the Erbb3 gene that serves as a valuable model for studying peripheral nervous system development. This ENU-generated heterozygous breeding strain produces homozygous mutant embryos that exhibit extreme defasciculation of dorsal root ganglia branches and complete loss of trigeminal mandibular branches before becoming lethal at E14.5. Available data demonstrates that this model provides researchers with a precise developmental window to investigate molecular mechanisms underlying peripheral nerve development.
Stage of Development
· This strain is available on Jax Lab’s repository:
o JAX # 013059 C3.B6-Erbb3m3329Ddg/J
Data Availability
· n/a
Publication
Janna Merte, Qiang Wang, Craig W. Vander Kooi, Sarah Sarsfield, Daniel J. Leahy, Alex L. Kolodkin and David D. Ginty. Journal of Neuroscience 21 April 2010, 30 (16) 5767-5775; https://doi.org/10.1523/JNEUROSCI.5061-09.2010
