Figure 7.

Genetic elimination of muscle spindle-derived GDNF results in selective loss of gamma motor neurons. (A) Size distributions of ChAT+ MNs in GDNF^FLOX/FLOX/Egr3^WT (no Cre) controls at P20 are comparable to wild types (lines). (B) ChAT+ MNs losses in the absence of spindle-derived GDNF (GDNF^FLOX/FLOX/Egr3^CRE/CRE mutants). Small ChAT+ MNs represent 32 ± 1% ( ± SEM) of all MNs in GDNF^FLOX/FLOX /Egr3^+/+ and 16.8 ± 1.1% in GDNF^FLOX/FLOX/Egr3^CRE/CRE animals. Inset shows a depletion at P5 comparable to Egr3^KO animals (see Figure 5F). (C) Similar loses in compound heterozygotes with one conditional and one null GDNF allele and a single copy of Egr3^CRE (GDNF^FLOX/LACZ/Egr3^CRE/+). Inset shows a normal size distribution in one animal carrying one wild type and one floxed GDNF allele and a single Egr3^CRE copy. (D) GDNF elimination from all muscle precursors using myf5^CRE/+ results in similar losses of small ChAT+ MNs. Large MN numbers are unaffected in conditional mutants by targeted removal of GDNF from spindles. (E) Comparison of the percentage of small MNs (<480 μm²) in different genotypes. No differences were detected between wild-type and homozygous GDNF^FLOX (no Cre) controls. Egr3^KO mutants and several conditional/floxed GDNF mutants crossed to Egr3^CRE or myf5^CRE showed significant depletions compared to wild-types and GDNF^FLOX (no Cre) controls (asterisks indicate P < 0.001 one-way ANOVA followed by P < 0.01 post-hoc Tukey comparisons). Depletion of small MNs in Egr3^KO animals were more pronounced than in other genotypes, but differences were not statistically significant. N's, number of animals analyzed in each genotype.