Cockayne Syndrome: The many challenges and approaches to understand a multifaceted disease

Vessoni, Alexandre Teixeira; Guerra, Camila Chaves Coelho; Kajitani, Gustavo Satoru; Nascimento, Livia Luz Souza; Garcia, Camila Carrião Machado

doi:10.1590/1678-4685-GMB-2019-0085

Alexandre Teixeira Vessoni ^**These authors contributed equally to this study

Washington University School of Medicine, Saint Louis, MO, USA.

Camila Chaves Coelho Guerra ^**These authors contributed equally to this study

Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Núcleo de Pesquisa em Ciências Biológicas & Departamento de Ciências Biológicas, Ouro Preto, MG, Brazil.

Gustavo Satoru Kajitani

Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Núcleo de Pesquisa em Ciências Biológicas & Departamento de Ciências Biológicas, Ouro Preto, MG, Brazil.

Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Microbiologia, São Paulo,SP, Brazil.

Livia Luz Souza Nascimento

Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Microbiologia, São Paulo,SP, Brazil.

Camila Carrião Machado Garcia

Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Núcleo de Pesquisa em Ciências Biológicas & Departamento de Ciências Biológicas, Ouro Preto, MG, Brazil.

https://orcid.org/0000-0002-5754-678X

Send correspondence to Camila Carrião Machado Garcia. Núcleo de Pesquisa em Ciências Biológicas & Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, 35400-000, Ouro Preto, MG, Brazil. E-mail: carriao.camila@gmail.com.

^*These authors contributed equally to this study

Author Contributions

ATV, CCCG, GSK, LLSN, CCMG wrote the manuscript, and all authors approved the final version.

The authors declare that there is no conflict of interest.

Associated Editor: Nicolas Hoch

*These authors contributed equally to this work.

Mouse model	Genetic background	Neurological abnormalities	Metabolic characteristics	Lifespan	Other reported features	References
Csb^m/m	C57BL/6J	Mild, progressive neurodegeneration with no behavioral phenotype, mild astro and microgliosis, hearing loss associated with loss of neurosensorial cells, late retinal degeneration	Increased metabolism and mitochondrial numbers, Progressive lipodistrophy	> 2 years	Increased skin cancer predisposition after UV exposure	Van der Horst et al., 1997; Jaarsma et al., 2011
Csa^-/-	C57BL/6J	Mild, progressive neurodegeneration with no behavioral phenotype, mild astro and microgliosis, hearing loss associated with loss of neurosensorial cells	Increased metabolism	> 2 years	Increased skin cancer predisposition after UV exposure	van der Horst et al., 2002; Gorgels et al, 2007; Jaarsma et al., 2011; Brace et al., 2016
Csb^m/m/Xpa^-/-	C57BL/6J; CBA/C57BL6/CD-1/129Ola hybrid	Profound early postnatal ataxia, abnormal cerebellar development and degeneration, loss of purkinjecells, progressive neurological dysfunction, motor coordination problems, early retinal degeneration	Severe post-natal growth deficiency, Severe lipodistrophy, decreased oxidative metabolism	3 weeks	Suppression of the GH/IGF1 somatotroph axis increased antioxidant responses, hypoglycemia	Murai et al., 2001, van der Pluijm et al., 2007; Jaarsma et al., 2011
Csb^-/- / Xpa^c/- CamKIIα-Cre	C57BL/6J	Progressive neurological dysfunction, Purkinje cell death, neurodegeneration, motor coordination problems starting at 6 months	Weight reduction in adult animals	90 weeks	-	Jaarsma et al., 2011
Csb^m/m/Xpc^-/-	C57BL/6J, 129Ola/C57BL/6J hybrid	Depletion of purkinje cells, neurodegeneration in cerebellum, motor coordination problems, dysmielination	Severe post-natal growth deficiency, Severe lipodistrophy	3 weeks	-	van der Pluijm et al., 2007; Laposa et al., 2007; Revet et al., 2012
Csb^m/m/Ogg1^-/-	C57BL/6J	No neurological phenotype has been observed	Not described	> 2 years	Accumulation of oxidative stress related DNA damage and mutations in various tissues	Osterod et al., 2002; Pastoriza-Gallego et al., ?2007; FusserFusser M, Nesse GJ, Khobta A, Xia N, Li H, Klungland A and Epe B (2011) Spontaneous mutagenesis in csbm/mogg1-/- mice is attenuated by dietary resveratrol. Carcinogenesis 32:80–85.et al., 2011
Csa^-/-/Xpa^-/-	C57BL/6J	Early, progressive neurological dysfunction, dysmyelination, abnormal cerebellar development and degeneration, motor coordination problems, severe astro and microgliosis	Post-natal growth deficiency, increased metabolism, severe lipodistrophy, senescence of fat tissue, no fat tissue inflammation	20 weeks	-	Brace et al., 2013; Brace et al., 2016
Xpg^-/-	C57BL/6J	Purkinje cell degeneration, cerebellum neurodegeneration	Severe post-natal growth deficiency, Severe lipodistrophy	3 weeks	Abnormalities of the gastro-intestinal tract, early fibroblast senescence	Harada et al., 1999; Sun et al., 2001; Barnhoorn et al., 2014
Xpg^-/-	C57BL6/FVB F1 hybrid	Purkinje cell death, neurodegeneration, motor coordination problems axonal spheroids, severe astrogliosis	Post-natal growth deficiency, loss of subcutaneous fat	18 weeks	Skeletal abnormalities, mild anisokaryosis, increased mean nuclear size of liver cells, supression of GH/IGF1 axis	Barnhoorn et al, 2014; Vermeij, 2016
Ercc1^-/-	Hybrid C57Bl/6/129	Early, progressive neurological dysfunction, neurodegeneration and motor coordination problems	Severe post-natal growth deficiency, decreased oxidative metabolism, severe lipodistrophy, increase in fat tissue inflammation	3 weeks	Liver nuclear abnormalities, p53 upregulation in liver and kidney, early fibroblast senescence	Mcwhir et al., 1993, Weeda et al., 1997
Ercc1^Δ/-	C57Bl6J/FVB hybrid	Early, progressive neurological dysfunction, myelin abnormalities, abnormal cerebellar development and degeneration, Motor coordination problems, severe astro and microgliosis	Post-natal growth deficiency, decreased oxidative metabolism, severe lipodistrophy, increase in fat tissue inflammation	22-25 weeks	Early fibroblast and vascular tissue senescence, reduced bone density	Weeda et al., 1997; NevedomskayaNevedomskaya E, Meissner A, Goraler S, De Waard M, Ridwan Y, Zondag G, Van Der Pluijm I, Deelder AM and Mayboroda OA (2010) Metabolic profiling of accelerated aging ERCC1d/- mice. J Proteome Res 9:3680–3687.et al., 2010; de Waard et al., 2010; DurikDurik M, Kavousi M, van der Pluijm I, Isaacs A, Cheng C, Verdonk K, Loot AE, Oeseburg H, Bhaggoe UM, Leijten F et al. (2013) Nucleotide Excision DNA Repair is Associated with Age-Related Vascular Dysfunction. Circulation 126:468–478.et al., 2012; Vermeij et al., 2016;

[1] Send correspondence to Camila Carrião Machado Garcia. Núcleo de Pesquisa em Ciências Biológicas & Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, 35400-000, Ouro Preto, MG, Brazil. E-mail: carriao.camila@gmail.com.

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Cockayne Syndrome: The many challenges and approaches to understand a multifaceted disease

Abstract