Fyn Knockout mouse models

Fyn, mouse ortholog of human FYN, encodes a Src family nonreceptor tyrosine kinase organized as a myristoylated and palmitoylated N-terminal membrane anchor followed by SH3, SH2 and kinase domains, held closed by CSK phosphorylation of the C-terminal tyrosine 531 and opened by CD45 or PTPN22 mediated dephosphorylation with activation loop autophosphorylation. In T cells FYN and LCK phosphorylate CD3 and zeta chain ITAMs to recruit ZAP70, while in neurons the FynB splice isoform phosphorylates NR2B to control NMDA receptor gating and phosphorylates tau at tyrosine 18, placing it downstream of amyloid beta and cellular prion protein signaling in Alzheimer disease models. Nulls are viable with impaired hippocampal long term potentiation and defective thymocyte selection, so constitutive alleles are workable. Src, Yes, Lck and Lyn are genuinely redundant in most lineages, so compound alleles are needed before claiming requirement. Choose conditional nulls for neuronal versus immune assignment and analog-sensitive knockins for acute chemical genetic inhibition.

Whole body loss of Fyn gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.