@article {715,
	title = {Spinster homolog 2 (spns2) deficiency causes early onset progressive hearing loss.},
	journal = {PLoS Genet},
	volume = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {e1004688},
	abstract = {<p>Spinster homolog 2 (Spns2) acts as a Sphingosine-1-phosphate (S1P) transporter in zebrafish and mice, regulating heart development and lymphocyte trafficking respectively. S1P is a biologically active lysophospholipid with multiple roles in signalling. The mechanism of action of Spns2 is still elusive in mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity and endocochlear potential (EP) from 2 to 3 weeks old. We found progressive degeneration of sensory hair cells in the organ of Corti, but the earliest defect was a decline in the EP, suggesting that dysfunction of the lateral wall was the primary lesion. In the lateral wall of adult mutants, we observed structural changes of marginal cell boundaries and of strial capillaries, and reduced expression of several key proteins involved in the generation of the EP (Kcnj10, Kcnq1, Gjb2 and Gjb6), but these changes were likely to be secondary. Permeability of the boundaries of the stria vascularis and of the strial capillaries appeared normal. We also found focal retinal degeneration and anomalies of retinal capillaries together with anterior eye defects in Spns2 mutant mice. Targeted inactivation of Spns2 in red blood cells, platelets, or lymphatic or vascular endothelial cells did not affect hearing, but targeted ablation of Spns2 in the cochlea using a Sox10-Cre allele produced a similar auditory phenotype to the original mutation, suggesting that local Spns2 expression is critical for hearing in mammals. These findings indicate that Spns2 is required for normal maintenance of the EP and hence for normal auditory function, and support a role for S1P signalling in hearing.</p>},
	keywords = {Age of Onset, Animals, Anion Transport Proteins, Anterior Eye Segment, Cochlea, Connexins, Ear, Inner, Hair Cells, Auditory, Hearing Loss, Lysophospholipids, Mice, Organogenesis, Sphingosine, Stria Vascularis, Zebrafish},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1004688},
	author = {Chen, Jing and Ingham, Neil and Kelly, John and Jadeja, Shalini and Goulding, David and Pass, Johanna and Mahajan, Vinit B and Tsang, Stephen H and Nijnik, Anastasia and Jackson, Ian J and White, Jacqueline K and Forge, Andrew and Jagger, Daniel and Steel, Karen P}
}
@article {149,
	title = {Mutations in prickle orthologs cause seizures in flies, mice, and humans.},
	journal = {American journal of human genetics},
	volume = {88},
	year = {2011},
	month = {2011 Feb 11},
	pages = {138-49},
	abstract = {<p>Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.</p>
},
	keywords = {Animals, Blotting, Western, Brain, Calcium, Carrier Proteins, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Epilepsies, Myoclonic, Female, Heterozygote, Humans, Immunoenzyme Techniques, In Situ Hybridization, Male, Mice, Mice, Knockout, Mutation, Nerve Tissue Proteins, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Seizures, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins},
	author = {Tao, Hirotaka and Manak, J Robert and Sowers, Levi and Mei, Xue and Kiyonari, Hiroshi and Abe, Takaya and Dahdaleh, Nader S and Yang, Tian and Wu, Shu and Chen, Shan and Fox, Mark H and Gurnett, Christina and Montine, Thomas and Bird, Thomas and Shaffer, Lisa G and Rosenfeld, Jill A and McConnell, Juliann and Madan-Khetarpal, Suneeta and Berry-Kravis, Elizabeth and Griesbach, Hilary and Saneto, Russell P and Scott, Matthew P and Antic, Dragana and Reed, Jordan and Boland, Riley and Ehaideb, Salleh N and El-Shanti, Hatem and Mahajan, Vinit B and Ferguson, Polly J and Axelrod, Jeffrey D and Lehesjoki, Anna-Elina and Fritzsch, Bernd and Slusarski, Diane C and Wemmie, John and Ueno, Naoto and Bassuk, Alexander G}
}
