Adolescent Idiopathic Scoliosis (AIS) is a spinal deformity that affects approximately 3 percent of human adolescents. Although the etiology and molecular basis of AIS is unclear, several genes such as POC5 have been identified as possible causes of the condition. In order to understand the role of POC5 in the pathogenesis of AIS, we investigated the subcellular localization of POC5 in cilia of cells over-expressing either the wild type (wt) or an AIS-related POC5 variant POC5 A429V . Mutation of POC5 was found to alter its subcellular localization and to induce ciliary retraction. Furthermore, we observed an impaired cell-cycle progression with the accumulation of cells in the S-phase in cells expressing POC5 A429V . Using immunoprecipitation coupled to mass spectrometry, we identified specific protein interaction partners of POC5, most of which were components of cilia and cytoskeleton. Several of these interactions were altered upon mutation of POC5. Altogether, our results demonstrate major cellular alterations, disturbances in centrosome protein interactions and cilia retraction in cells expressing an AIS-related POC5 mutation. Our study suggests that defects in centrosomes and cilia may underlie AIS pathogenesis.

SUMMARY In the horse, gamma‐glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/l. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at —30°C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse. RÉSUMÉ Chez le cheval la gamma glutamyl transferase a été localisée surtout dans les reins, le foie et le pancréas. Les lésions rénales entrainent une fuite des enzymes dans l'urine. On peut donc penser que l'élévation du taux sérique proviendrait du foie ou du pancréas. Dans le sang, la GGT peut être mesurée dans le sang total ou dans le serum. Les valeurs moyennes chez 58 chevaux furent de 12 unités par litre. Ce taux ne fut affecté ni par une légère dilution ni par une légère hémolyse et l'activité enzymatique fut seulement légèrement diminuée après une conservation à—30°. La relative specificité hépatique de cette enzyme et sa mesure facile permettent de l'utiliser dans l'exploration des troubles hépatiques. ZUSAMMENFASSUNG γGT wurde beim Pferd vor allem in den Nieren, der Leber und im Pankreas gefunden. Weil Nierenläsionen gefolgt werden von einer Ausscheidung des Enzyms über den Urin, darf angenommen werden, dass erhöhte Serumwerte aus Leber oder Pankreas stammen. Im Blut kann die γGT entweder im Plasma oder Serum bestimmt werden. Die mittlere Aktivität betrug bei 58 Pferden 12 U/Liter. Dieser Wert wurde nicht beeinflusst durch mässige Verdünnung oder leichte Haemolyse und die Aufbewahrung bei —30°C führte nur zu einem leichten Aktivitätsabfall. Die relative hepatische Spezifität dieses Enzyms und seine leichte Bestimmbarkeit lassen es als potentiell sehr nützlichen Parameter zur Erfassung von Lebererkrankungen beim Pferd erscheinen.

The physiological role and the regulation of ADGRG7 are not yet elucidated. The functional involvement of this receptor was linked with different physiological process such as reduced body weight, gastrointestinal function and recently, a gene variant in ADGRG7 was observed in patients with adolescent idiopathic scoliosis. Here, we identify the ADGRG7 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that ADGRG7 expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. ADGRG7 promoter studies indicate the presence of an ERα response half site in close vicinity of a specificity protein 1 (SP1) binding site. Mutation of the SP1 site completely abrogated the response to E2, indicating its essential requirement. ChIP confirmed the binding of SP1 and ERα to the ADGRG7 promoter. Our results identify the ADGRG7 gene as an estrogen-responsive gene under the control of ERα and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of ADGRG7.

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