Ultrastructural changes in endometrial desmosomes of desmoglein 2 mutant mice

Abstract

The intercellular binding of desmosomal junctions is mediated by cadherins of the desmoglein (Dsg) and desmocollin (Dsc) type. Dsg2 mutant mice with deletion of a substantial segment of the extracellular EC1-EC2 domain, which is believed to participate in homo- and heterophilic desmosomal cadherin interactions, develop cardiac fibrosis and ventricular dilation. Widening of the intercellular cleft and complete intercalated disc ruptures can be observed in the hearts of these mice. Since a reduced litter size of homozygous Dsg2 mutant mice was noted and a functional correlation between desmosomes and embryo implantation has been deduced from animal studies, we looked for an alteration of desmosomes in uterine endometrial epithelium. Shape and number of desmosomes as well as the expression of Dsg2 and the desmosomal plaque protein desmoplakin (Dsp) were investigated by electron microscopy and immunohistochemistry in 12 oestrous-dated mice (7 wild type and 5 homozygous Dsg2 mutant mice) at the age of 9-17 weeks. The immunohistochemical detection of Dsg2 was diminished in the mutants and the number of desmosomes was significantly reduced as revealed by electron microscopy. In addition, the intercellular desmosomal space measured in electron micrographs was considerably widened in the Dsg2 mutants. The increased intercellular spacing can be explained by the partial deletion of the extracellular EC1-EC2 domain of Dsg2. Whether these changes explain the reduced number of offspring of homozygous Dsg2 mutant mice remains to be further investigated.

Dynamic Loading of Human Engineered Heart Tissue Enhances Contractile Function and Drives Desmosome-linked Disease Phenotype

“…In contrast, 8x dyn-EHTs formed using DSPmut cardiomyocytes resulted in tissue lengthening and reduced contractile stress generation. Furthermore, in DSPmut tissues we found reduced amount and expression of desmosomes compared to control, which has also been observed in patients and small animal studies with desmosomal defects (5,71). Taken together, these findings suggest that 3D dynamic mechanical loading of EHTs may be better suited to investigate heart diseases with a cardiomyocytejunctional or cytoskeletal component.…”

Genetic Animal Models for Arrhythmogenic Cardiomyopathy

“…AAV = adeno associated virus; bp = base pair, cKO = cardiac specific knockout; ciKO = cardiac specific, inducible knockout; cidKO = cardiac specific, inducible double knockout; gKO = global knockout; het = heterozygous; hom = homozygous; KD = knockdown; KI = knock-in. [1] ( Ruiz et al, 1996 ); [2] ( Bierkamp et al, 1996 ); [3] ( Gallicano et al, 1998 ); [4] ( Eshkind et al, 2002 ); [5] ( Grossmann et al, 2004 ); [6] ( Garcia-Gras et al, 2006 ; Cheedipudi et al, 2019 ); [7] ( Yang et al, 2006 ); [8] ( Kirchhof et al, 2006 ; Fabritz et al, 2011 ); [9] ( Heuser et al, 2006 ); [10] ( Pilichou et al, 2009 ; Rizzo et al, 2012 ); [11] ( Martin et al, 2009 ); [12] ( Krusche et al, 2011 ; Kant et al, 2012 ; Buck et al, 2018 ); [13] ( Lombardi et al, 2011 ); [14] ( Li et al, 2011 ); [15] ( Li et al, 2011 ); [16] ( Cerrone et al, 2012 ; Leo-Macias et al, 2015 ); [17] ( Gomes et al, 2012 ); [18] ( Swope et al, 2012 ); [19] ( Moriarty et al, 2012 ); [20] ( Lyon et al, 2014 ); [21] ( Rimpler, 2014 ); [22] ( Asimaki et al, 2014 ); [23] ( Cruz et al, 2015 ); [24] ( Mezzano et al, 2016 ); [25] ( Herbert Pratt et al, 2015 ); [26] ( Kant et al, 2015 ); [27] ( Zhang et al, 2015 ); [28] ( Moncayo-Arlandi et al, 2016 ); [29] ( Chelko et al, 2016 ); [30] ( Cerrone et al, 2017 ); [31] ( Brodehl et al, 2017 ); [32] ( Calore et al, 2019 ); [33] ( Giuliodori et al, 2018 ); [34] ( Hamada et al, 2020 ).…”

“…AAV = adeno associated virus; bp = base pair, cKO = cardiac specific knockout; ciKO = cardiac specific, inducible knockout; cidKO = cardiac specific, inducible double knockout; gKO = global knockout; het = heterozygous; hom = homozygous; KD = knockdown; KI = knock-in. [1] (Ruiz et al, 1996); [2] (Bierkamp et al, 1996); [3] (Gallicano et al, 1998); [4] (Eshkind et al, 2002); [5] (Grossmann et al, 2004); [6] (Garcia-Gras et al, 2006;Cheedipudi et al, 2019); [7] (Yang et al, 2006); [8] (Kirchhof et al, 2006;Fabritz et al, 2011);[9] (Heuser et al, 2006); [10] (Pilichou et al, 2009;Rizzo et al, 2012); [11] (Martin et al, 2009); [12] (Krusche et al, 2011;Kant et al, 2012;Buck et al, 2018); [13] (Lombardi et al, 2011); [14] [15] [16] (Cerrone et al, 2012;Leo-Macias et al, 2015); [17] (Gomes et al, 2012) (Hamada et al, 2020). (Gerull et al, 2019).…”

Neuronal-Glial Membrane Contacts During Pessimal Electrical Stimulation

“…1в), обладающей богатой двухсторонней примембранной бахромой. Десмосомы имеют небольшую длину, как у активных зон синапсов и поддерживаются микротрубочками [26], адгезионными белками и кадгеринами [27]. Десмосомы часто путают с активными зонами синапсов [28].…”

“…Кроме двухсторонних широких околомембранных слоев бахромы липидный бислой внутри десмосомы на 10% толще, чем соседние участки плазматической мембраны [29]. Внутридесмосомная щель может быть расширена до 220-350 ангстрем по сравнению с обычной межклеточной щелью [27]. Их структура способна собираться и разбираться [30].…”