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Central Precocious Puberty Disease

A novel model of central precocious puberty disease: Paternal MKRN3 gene–modified rabbit


Background


Makorin ring finger protein 3 gene (MKRN3) gene mutation is the most common genetic cause of central precocious puberty (CPP) in children. Due to the lack of ideal MKRN3-modified animal model (MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice), the related research is limited.

Methods


Therefore, the MKRN3-modified rabbit was developed using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing technology. The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.

Results


The first estrus of MKRN3-modified female rabbits was observed ~27 days earlier than that of wild-type female rabbits, with a typical CPP phenotype. This study found increased gonadotropin releasing hormone (GnRH) and decreased gonadotropin inhibiting hormone (GnIH) in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation. Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation, it found some differentially expressed genes and potential pathways through transcriptome sequencing.

Central precocious puberty (CPP) is a disease that causes precocious puberty in children due to premature activation of the hypothalamic–pituitary–gonadal axis (HPG axis). The incidence of CPP is 1/5000–1/10 000, 5–10 times more in girls than boys. CPP seriously endangers the physical and mental health of children, leading to short stature, obesity, low self-esteem, and social barriers in adulthood, as well as increased risk of cardiovascular disease, metabolic disease, and cancer. CPP has a certain genetic predisposition. In 2013, the New England Journal of Medicine first reported that makorin ring finger protein 3 (MKRN3) gene can lead to CPP..In CPP with familial inheritance, the incidence of MKRN3 mutation is the highest, about 30%.

The human MKRN3 gene is located on chromosome 15q11.2-13 and has only one exon. It is a maternal imprinting gene located at the Prader Willi syndrome locus and can be expressed only in the paternal allele. Therefore, the patient inherits the MKRN3 mutation of the father, which can cause CPP. At present, it has been found that a variety of MKRN3 site mutations can cause CPP. The level of mkrn3 protein in the peripheral blood of CPP patients is significantly lower than that of normal people.

Conclusions


This study established a novel CPP model: paternal MKRN3 gene-modified rabbit. It is hoped that the establishment of this model will help researchers better understand, treat, and prevent CPP in the future.

precocious puberty, delayed puberty, hormonal imbalance, hypogonadism, Turner syndrome, Klinefelter syndrome, polycystic ovary syndrome (PCOS), thyroid disorders, growth hormone deficiency, congenital adrenal hyperplasia, androgen insensitivity syndrome, pituitary tumors, menstrual irregularities, gynecomastia, adolescent obesity, insulin resistance, hyperprolactinemia, acne vulgaris, mood disorders

PubertyDisorders, #HormonalImbalance, #PrecociousPuberty, #DelayedPuberty, #PCOS, #TurnerSyndrome, #KlinefelterSyndrome, #GrowthHormoneDeficiency, #AdolescentHealth, #ThyroidDisorders, #CongenitalAdrenalHyperplasia, #Hypogonadism, #Gynecomastia, #InsulinResistance, #MoodDisorders, #Amenorrhea, #PituitaryDisorders, #TeenHealth, #PubertyAwareness, #HormoneTherapy


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