Phenotype Image Detail

Image

Caption

Severe neuron loss in the motor cortex and cerebellum in Zfyve26^tm1.1Cahb/Zfyve26^tm1.1Cahb (KO) mice. (A-B) The brain was smaller in 16-month old mutant compared to wild-type (WT) mice. Scale bars: 2 mm. (C) Progressive reduction of brain weight in mutant mice (n = 4; 2-way ANOVA; **: p<0.001). (D, E) Astrogliosis and loss of NeuN-positive neuronal cells in the motor cortex of 16-month-old mutant mice. Hoechst-33258 (blue; nuclei), GFAP (green; astrocyte marker), and NeuN (red; neuronal marker) staining of the motor cortex at 16 months of age from WT (D) and mutant (E) mice. Individual cortical layers are labeled (I-VI). Scale bars: 100 um. (F) Quantification of NeuN-positive cells per layer revealed a significant reduction of neurons from layers V-VI of the motor cortex in 16-month-old mutant mice p<0.001). (G-H) Cerebellar sections stained for GFAP (green), Calbindin (red, Purkinje cell marker), and Hoechst-33258 (blue) revealed a severe loss of Purkinje cells in 16-month-old mutant mice. Scale bars: 100 um. GCL: granule cell layer, PCL: Purkinje cell layer, ML: molecular layer. (I) In mutant mice Purkinje cells were drastically reduced at 16 months (2-way ANOVA; ***: p<0.0001), but not at 2 months of age. (J-K) Semithin sections of the lumbar corticospinal tract illustrates the reduction in the number of large diameter axons in 16-month-old knockout mice. Scale bars: 20 um. (L) Transmission electron microscopy of a degenerating axon in a mutant mouse. Scale bar: 1 um. (M, N) Delayed outgrowth of Tau-positive axons of cultured motoneurons isolated from KO embryos compared to WT mice. (Student's t-test; **: p<0.001). Scale bar in M: 40 um. (O) The number of axonal branches in cultured motoneurons did not differ between genotypes. Error bars represent SEM. (Student's t-test; n.s.: not significant).

Copyright

This image is from Khundadze M, PLoS Genet 2013;9(12):e1003988, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:223127

Associated Alleles

Symbol	Name
Zfyve26^tm1.1Cahb	zinc finger, FYVE domain containing 26; targeted mutation 1.1, Christian A Hubner

Associated Genotypes

Allelic Composition	Genetic Background
Zfyve26^tm1.1Cahb/Zfyve26^tm1.1Cahb	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6