Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics
Abstract
:1. Introduction
2. Discussion
2.1. Genetics
2.2. PWS-Like Syndromes: 6q16 Deletions
2.3. Non Imprinted PWS Genes
2.4. Mouse Models
2.5. The Zebrafish Model: Conserved Neuroanatomy and Physiology
2.6. Technologies for Phenotypic Analysis: PWS Endophenotypes
2.7. Strategies for Targeted Gene Manipulation
2.8. Approaches for Gene Discovery in Zebrafish
2.9. Pharmacogenomic Methods in Zebrafish
2.10. Fast Track to PWS Pharmacotheraputics
3. Conclusions
Acknowledgments
Conflicts of Interest
References
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Medical Symptom | Age of Onset | Treatment Options |
---|---|---|
hypotonia and feeding difficulties | 0–9 months | feeding assistance, nasogastric tubes |
hyperphagia | 4.5–8 years | behavioral therapy |
short stature | puberty | GH therapy, allows patients to reach full adult height |
hypoplastic genitalia | birth | hormonal replacement therapy |
dysmorphic features | birth | none |
sleep-disordered breathing and daytime hypersomnolence | childhood to adolescence (Nixon and Brouillette) | adenotonsillectomy, nocturnal ventilation, weight control, and behavioral interventions |
cognitive disability | childhood | none |
skin picking and obsessive behavior | 5 years | behavioral therapy |
oppositional behavior and tantrums | 5 years | behavioral therapy and psychiatric drugs |
Human | Mouse | % aa | Zebrafish | % aa | Chr. |
---|---|---|---|---|---|
FRAT1; Chr10 * | Peg12 | 70 | gbp + | 63 | 16 |
MKRN3 | Mkrn3 | 63 | mkrn1 | 48 | 4 |
MAGEL2 | Magel2 | 53 | ndnl2 &,+ | 48 | 23 |
NDN | Ndn | 82 | ndnl2 &,+ | 40 | 23 |
NPAP1 | Pom121; Chr5 * | 28 | pom121 + | 24 | 10 |
SNRPN | Snrpn | 100 | snrpb | 93 | 6 |
SNORD107 | Snord 107 | - | |||
SNORD64 | Snord 64 | - | |||
SNORD116@27 | Snord116@27 | - | |||
SNORD115@41 | Snord115@130 | - | |||
SNORD108 | - | - | |||
SNORD109A | - | - | |||
SNORD109B | - | - |
Failure to Thrive/Early Fatality | No Observable Abnormal Phenotype |
---|---|
Maternal duplication and paternal deletion in PWS region [36] | Deletion of exon 1 of Snrpn [39] |
6.8 Mb deletion spanning PWS and AS regions [37] | Deletion of Snrpn exon 2 [40] |
Deletion spanning from Snrpn to Ube3a [40] | Double deletion of Snrpn exon 2 and Ube3a [40] |
Deletion of Snrpn exons 1–6 and distal portion of IC [41] | Deletion of Snrpn exon 6, parts of exons 5 and 7 [41] |
4.8 kB deletion removing exon 1 of Snrpn and most of the differentially methylated region 1 (DMR1) [39] |
Endo-Phenotype | Ndn [43] | Magel2 [42,44,46] | Snord116 [45] |
---|---|---|---|
Reduced oxytocin expression | Yes | - | - |
Postnatal growth retardation | X | Yes | Yes |
Increased anxiety | - | Yes | Yes |
Respiratory distress | Yes | - | - |
Skin scraping | Yes | - | - |
Improved spatial memory and learning | Yes | X | X |
Altered circadian output | - | Yes | - |
Impaired fertility | X | Yes | X |
Increased fat mass | X | Yes | X |
Hyperphagia | - | X | Yes |
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Spikol, E.D.; Laverriere, C.E.; Robnett, M.; Carter, G.; Wolfe, E.; Glasgow, E. Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics. Diseases 2016, 4, 13. https://doi.org/10.3390/diseases4010013
Spikol ED, Laverriere CE, Robnett M, Carter G, Wolfe E, Glasgow E. Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics. Diseases. 2016; 4(1):13. https://doi.org/10.3390/diseases4010013
Chicago/Turabian StyleSpikol, Emma D., Caroline E. Laverriere, Maya Robnett, Gabriela Carter, Erin Wolfe, and Eric Glasgow. 2016. "Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics" Diseases 4, no. 1: 13. https://doi.org/10.3390/diseases4010013