Phenotype Image Detail

Image

Caption

Insufficient myelination resulting from loss of Gjc2 (Cx47) function is largely, although not completely, compensated in adult Gjc2⁺/Gjc2^tm2.1Kwi (Cx47^+/M282T) and Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi (Cx47^M282T/M282T) mice. Additional deletion of Gjb1 (Cx32) in homozygous Cx47^M282T (Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi Gjb1^tm1Kwi/Y) mice resulted in severe myelin malformation, astrogliosis and microglia activation. A, Immunohistochemical analysis on 25 um sagittal cerebellar slices obtained from 90-day-old animals yielded strong myelin staining in the granular layer of wild-type (Cx47^+/+) mice. D, G and J, Only few MBP-positive fibers attaining the Purkinje cell layer were found in corresponding regions of Gjc2⁺/Gjc2^tm2.1Kwi (Cx47^+/M282T), Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi (Cx47^M282T/M282T) and Gjc2⁺/Gjc2^tm2.1Kwi Gjb1^tm1Kwi/Y (Cx47^+/M282T/Cx32^Y/-) mice. M, MBP immunohistochemical signals were very weak in Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi Gjb1^tm1Kwi/Y (Cx47^M282T/M282T/Cx32^Y/-) animals and appeared like debris in the granular layer. B, E, H, K and N, GFAP staining on cerebellar slices of all five genotypes revealed astrogliosis only in Cx47^M282T/M282T/Cx32^Y/- animals (N) whereas Cx47^+/+, Cx47^+/M282T, Cx47^M282T/M282T and Cx47^+/M282T/Cx32^Y/- mice did not display increased GFAP expression in the cerebellar white matter. H inset, Like P10 mice adult Cx47^M282T/M282T mice harboured fewer GFAP-positive cells in the granular layer compared to Cx47^+/+ and Cx47^+/M282T mice. Arrows indicate the transition of white matter to the granule cell layer. Signals of GFAP-positive Begmann glia processes were used as internal control for staining intensities. O, Furthermore, considerable numbers of Iba1 expressing activated microglial cells were present in Cx47^M282T/M282T/ Cx32^Y/- cerebellar white matter. All other genotypes investigated did not display microglia with increased Iba1 exression in cerebellar tissue. Auxiliary lines indicate the granular and Purkinje cell layer transition. Scale bars: A-O, 200 um; insets MBP and GFAP stainings, 50 um; insets Iba1 stainings, 25 um.

Copyright

This image is from Tress O, PLoS Genet 2011 Jul;7(7):e1002146, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:174197

Associated Alleles

Symbol	Name
Gjb1^tm1Kwi	gap junction protein, beta 1; targeted mutation 1, Klaus Willecke
Gjc2^tm2.1Kwi	gap junction protein, gamma 2; targeted mutation 2.1, Klaus Willecke

Associated Genotypes

Allelic Composition	Genetic Background
Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi	involves: C57BL/6 * SJL
Gjb1^tm1Kwi/Y Gjc2^tm2.1Kwi/Gjc2^tm2.1Kwi	involves: 129S4/SvJae * C57BL/6 * SJL