appear smaller than their littermates, reminiscent of the short stature observed in patients with AHO. Furthermore, the exon 2 knockout mice prove to be a good model of PTH resistance. Reflecting the tissue-specific silencing of paternal Gsα in the proximal tubule, PTH-resistance, characterized by hypocalcemia, hyperphosphatemia, and elevated serum PTH, is present only after maternal inheritance of the disrupted allele [40]. In addition, PTH stimulation of proximal tubule extracts from mice with the maternal disruption, but not with the paternal disruption, fail to increase cAMP levels. Similar to the observations in PHP-Ia patients, the urine concentrating ability of the kidney in response to vasopressin is unimpaired in both the maternal and the paternal knockouts. Hence, although the findings resulted from the disruption of exon 2 are rather complicated due to the use of this exon by not only Gsα but also several other GNAS products (particularly XLαs), this animal model is able to phenocopy PHP-Ia to a significant extent.
