Dataset Information

High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism.

ABSTRACT: Expression of HMGA2 is strongly associated with body size and growth in mice and humans. In mice, inactivation of one or both alleles of Hmga2 results in body-size reductions of 20% and 60%, respectively. In humans, microdeletions involving the HMGA2 locus result in short stature, suggesting the function of the HMGA2 protein is conserved among mammals. To test this hypothesis, we generated HMGA2-deficient pigs via gene editing and somatic cell nuclear transfer (SCNT). Examination of growth parameters revealed that HMGA2-/+ male and female pigs were on average 20% lighter and smaller than HMGA2+/+ matched controls (P < 0.05). HMGA2-/- boars showed significant size reduction ranging from 35 to 85% of controls depending on age (P < 0.05), and organ weights were also affected (P < 0.05). HMGA2-/+ gilts and boars exhibited normal reproductive development and fertility, while HMGA2-/- boars were sterile due to undescended testes (cryptorchidism). Crossbreeding HMGA2-/+ boars and gilts produced litters lacking the HMGA2-/- genotype. However, analysis of day (D) D40 and D78 pregnancies indicated that HMGA2-/- fetuses were present at the expected Mendelian ratio, but placental abnormalities were seen in the D78 HMGA2-/- concepti. Additionally, HMGA2-/- embryos generated by gene editing and SCNT produced multiple pregnancies and viable offspring, indicating that lack of HMGA2 is not lethal per se. Overall, our results show that the effect of HMGA2 with respect to growth regulation is highly conserved among mammals and opens up the possibility of regulating body and organ size in a variety of mammalian species including food and companion animals.

SUBMITTER: Chung J

PROVIDER: S-EPMC6003518 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism.

Chung Jaewook J Zhang Xia X Collins Bruce B Sper Renan B RB Gleason Katherine K Simpson Sean S Koh Sehwon S Sommer Jeffrey J Flowers William L WL Petters Robert M RM Piedrahita Jorge A JA

Proceedings of the National Academy of Sciences of the United States of America 20180507 21

Expression of HMGA2 is strongly associated with body size and growth in mice and humans. In mice, inactivation of one or both alleles of Hmga2 results in body-size reductions of 20% and 60%, respectively. In humans, microdeletions involving the HMGA2 locus result in short stature, suggesting the function of the HMGA2 protein is conserved among mammals. To test this hypothesis, we generated HMGA2-deficient pigs via gene editing and somatic cell nuclear transfer (SCNT). Examin ...[more]

PMID: 29735702

Similar Datasets

Project description:IntroductionNeonates with cardiorespiratory compromise at delivery are at substantial risk of hypoxic neurologic injury and death. Though mitigation strategies such as ex-utero intrapartum treatment (EXIT) exist, the competing interests of neonatal beneficence, maternal non-maleficence, and just distribution of resources require consideration. Due to the rarity of these entities, there are few systematic data to guide evidence-based standards. This multi-institutional, interdisciplinary approach aims to elucidate the current scope of diagnoses that might be considered for such treatments and examine if treatment allocation and/or outcomes could be improved.MethodsAfter IRB approval, a survey investigating diagnoses appropriate for EXIT consultation and procedure, variables within each diagnosis, occurrence of maternal and neonatal adverse outcomes, and instances of suboptimal resource allocation in the last decade was sent to all North American Fetal Treatment Network center representatives. One response was recorded per center.ResultsWe received a 91% response rate and all but one center offer EXIT. Most centers (34/40, 85%) performed 1-5 EXIT consultations per year and 17/40 (42.5%) centers performed 1-5 EXIT procedures in the last 10 years. The diagnoses with the highest degree of agreement between centers surveyed to justify consultation for EXIT are head and neck mass (100%), congenital high airway obstruction (90%), and craniofacial skeletal conditions (82.5%). Maternal adverse outcomes were noted in 7.5% of centers while neonatal adverse outcomes in 27.5%. A large percentage of centers report cases of suboptimal selection for risk mitigation procedures and several centers experienced adverse neonatal and maternal outcomes.ConclusionThis study captures the scope of EXIT indications and is the first to demonstrate the mismatch in resource allocation for this population. Further, it reports on attributable adverse outcomes. Given suboptimal allocation and adverse outcomes, further examination of indications, outcomes, and resource use is justified to drive evidence-based protocols.

Dataset Information

High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism.

Publications

High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets