Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1δ/− mouse

Spoor, Marcella; Nagtegaal, A. Paul; Ridwan, Yanto; Borgesius, Nils Z.; Alphen, Bart van; Pluijm, Ingrid van der; Hoeijmakers, Jan H.J.; Frens, Maarten A.; Borst, Jannie

doi:10.1016/j.mad.2011.12.003

Cited by 12 publications

(5 citation statements)

References 73 publications

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“…Further, Category 03 gene Nmnat1 encodes an enzyme that synthesizes nicotinamide adenine dinucleotide in the nucleus, which may regulate the large-scale polyADP-ribosylation of protein targets at sites of DNA damage [402]. Mutations in the genes encoding these proteins all result in PR cell loss [230,384,385,400,401,[403][404][405][406][407][408][409][410][411]. Mutations in five of these genes as included in Figure 6 (Cwc27, Ercc1, Ercc6, Sirt6, and Ubb) caused moderate to slow progression of PR cell loss (D 50 ≥ 2 months), consistent with a steady accumulation of unresolved DNA damage with age.…”

Section: Category 10: Dna Repair Rna Biogenesis and Protein Modificmentioning

confidence: 99%

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Collin

Gogna

Chang

et al. 2020

Cells

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Inherited retinal degeneration (RD) leads to the impairment or loss of vision in millions of individuals worldwide, most frequently due to the loss of photoreceptor (PR) cells. Animal models, particularly the laboratory mouse, have been used to understand the pathogenic mechanisms that underlie PR cell loss and to explore therapies that may prevent, delay, or reverse RD. Here, we reviewed entries in the Mouse Genome Informatics and PubMed databases to compile a comprehensive list of monogenic mouse models in which PR cell loss is demonstrated. The progression of PR cell loss with postnatal age was documented in mutant alleles of genes grouped by biological function. As anticipated, a wide range in the onset and rate of cell loss was observed among the reported models. The analysis underscored relationships between RD genes and ciliary function, transcription-coupled DNA damage repair, and cellular chloride homeostasis. Comparing the mouse gene list to human RD genes identified in the RetNet database revealed that mouse models are available for 40% of the known human diseases, suggesting opportunities for future research. This work may provide insight into the molecular players and pathways through which PR degenerative disease occurs and may be useful for planning translational studies.

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Section: Category 10: Dna Repair Rna Biogenesis and Protein Modificmentioning

confidence: 99%

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Collin

Gogna

Chang

et al. 2020

Cells

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“…However, cell death may be at the expense of tissue homeostasis, the loss of which induces hypocellularity and contributes to age-related pathology. Clear examples are the irreversible loss of hair cells in the cochlea of the ear and loss of photoreceptor cells in the retina, which directly causes loss of hearing and vision, respectively (78). However, rare somatic stem cells, defined by their capacity to self-renew and their ability to differentiate into mature cells with tissue-specific characteristics, are present in many adult tissues and play a crucial role to replace cells lost to cellular turnover, injury or disease.…”

Section: Dna Damage-induced Loss Of Tissue Homeostasismentioning

confidence: 99%

Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options

Vermeij

Hoeijmakers

Pothof

2016

Annu. Rev. Pharmacol. Toxicol.

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100

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Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology.

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“…The ABR was used to obtain hearing level thresholds as described previously (Spoor et al 2012). Briefly, hearing level thresholds were measured in response to 1 millisecond tone pips at 4, 8, 16 and 32 kHz at intensities ranging from −10 to 110 dB sound pressure level (SPL; re 20 μPa) at 5-dB resolution.…”

Section: Auditory Brainstem Responsementioning

confidence: 99%

A novel QTL underlying early‐onset, low‐frequency hearing loss in BXD recombinant inbred strains

Nagtegaal

Spijker

Crins

et al. 2012

Genes Brain and Behavior

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The DBA/2J inbred strain of mice has been used extensively in hearing research as it suffers from earlyonset, progressive hearing loss. Initially, it mostly affects high frequencies, but already at 2-3 months hearing loss becomes broad. In search for hearing loss genes other than Cadherin 23 (otocadherin) and fascin-2, which make a large contribution to the high-frequency deficits, we used a large set of the genetic reference population of BXD recombinant inbred strains. For frequencies 4, 8, 16 and 32 kHz, auditory brainstem response hearing thresholds were longitudinally determined from 2-3 up to 12 weeks of age. Apart from a significant, broad quantitative trait locus (QTL) for high-frequency hearing loss on chromosome 11 containing the fascin-2 gene, we found a novel, small QTL for low-frequency hearing loss on chromosome 18, from hereon called ahl9. Realtime quantitative polymerase chain reaction of organs of Corti, isolated from a subset of strains, showed that a limited number of genes at the QTL were expressed in the organ of Corti. Of those genes, several showed significant expression differences based on the parental line contributing to the allele. Our results may aid in the future identification of genes involved in low-frequency, early-onset hearing loss.

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Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1δ/− mouse

Cited by 12 publications

References 73 publications

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options

A novel QTL underlying early‐onset, low‐frequency hearing loss in BXD recombinant inbred strains

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