PDF(Pubmed)
Abstract：
UNASSIGNED: The glial cells missing 2 (GCM2) gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of GCM2, p.Y394S, has been reported in patients with familial primary hyperparathyroidism.
UNASSIGNED: To determine whether the GCM2 p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model.
UNASSIGNED: CRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous Gcm2 variant p.Y392S that corresponds to the human GCM2 p.Y394S variant. Wild-type (Gcm2+/+) and germline heterozygous (Gcm2+/Y392S) mice were evaluated for serum biochemistry and parathyroid gland morphology.
UNASSIGNED: Gcm2 +/Y392S mice did not show any change compared to Gcm2+/+ mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size.
UNASSIGNED: The mouse model of the p.Y392S variant of Gcm2 shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of Gcm2+/Y392S mice to study the effect of this variant of Gcm2 on early events in parathyroid gland development will be of interest.
UNASSIGNED: To determine whether the GCM2 p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model.
UNASSIGNED: CRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous Gcm2 variant p.Y392S that corresponds to the human GCM2 p.Y394S variant. Wild-type (Gcm2+/+) and germline heterozygous (Gcm2+/Y392S) mice were evaluated for serum biochemistry and parathyroid gland morphology.
UNASSIGNED: Gcm2 +/Y392S mice did not show any change compared to Gcm2+/+ mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size.
UNASSIGNED: The mouse model of the p.Y392S variant of Gcm2 shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of Gcm2+/Y392S mice to study the effect of this variant of Gcm2 on early events in parathyroid gland development will be of interest.
摘要：
■神经胶质细胞缺失2（GCM2）基因作为转录因子，对甲状旁腺发育至关重要，该基因中的变异与2种甲状旁腺疾病相关：纯合子种系失活变异患者的孤立性甲状旁腺功能减退和杂合子种系激活变异患者的原发性甲状旁腺功能亢进。GCM2的复发性种系激活错义变体，p.Y394S，已报道家族性原发性甲状旁腺功能亢进患者。
■确定GCM2p.Y394S错义变体是否在小鼠模型中引起甲状旁腺过度活跃和增大。
使用CRISPR/Cas9基因编辑技术来产生具有对应于人GCM2p.Y394S变体的种系杂合Gcm2变体p.Y392S的小鼠模型。评估野生型(Gcm2+/+)和种系杂合(Gcm2+/Y392S)小鼠的血清生物化学和甲状旁腺形态。
■Gcm2+/Y392S小鼠与Gcm2+/+小鼠相比，血清钙和甲状旁腺激素水平没有任何变化，甲状旁腺组织学,细胞增殖，或甲状旁腺大小。
■Gcm2的p.Y392S变体的小鼠模型表明，该变体在小鼠中具有耐受性，因为它不会增加甲状旁腺细胞增殖和循环钙或PTH水平。对Gcm2+/Y392S小鼠的进一步研究以研究Gcm2的这种变体对甲状旁腺发育中的早期事件的影响将是感兴趣的。
■确定GCM2p.Y394S错义变体是否在小鼠模型中引起甲状旁腺过度活跃和增大。
使用CRISPR/Cas9基因编辑技术来产生具有对应于人GCM2p.Y394S变体的种系杂合Gcm2变体p.Y392S的小鼠模型。评估野生型(Gcm2+/+)和种系杂合(Gcm2+/Y392S)小鼠的血清生物化学和甲状旁腺形态。
■Gcm2+/Y392S小鼠与Gcm2+/+小鼠相比，血清钙和甲状旁腺激素水平没有任何变化，甲状旁腺组织学,细胞增殖，或甲状旁腺大小。
■Gcm2的p.Y392S变体的小鼠模型表明，该变体在小鼠中具有耐受性，因为它不会增加甲状旁腺细胞增殖和循环钙或PTH水平。对Gcm2+/Y392S小鼠的进一步研究以研究Gcm2的这种变体对甲状旁腺发育中的早期事件的影响将是感兴趣的。
