Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome

Bischof, Jocelyn M.; Stewart, Colin L.; Wevrick, Rachel

doi:10.1093/hmg/ddm225

Cited by 179 publications

(203 citation statements)

References 35 publications

Supporting

Mentioning

191

Contrasting

Order By: Relevance

“…Adult mice deficient in Magel2 have markedly reduced activity, reduced metabolism, increased adiposity after weaning, behavioural problems and impaired male fertility (Bischof et al, 2007;Kozlov et al, 2007). Magel2-deficient mice have 50% neonatal mortality with impaired suckling onset behaviour and subsequently impaired feeding (Schaller et al, 2010).…”

Section: The Evolution Of Imprinting In the Post-natal Mammalmentioning

confidence: 99%

Post-natal imprinting: evidence from marsupials

et al. 2014

View full text Add to dashboard Cite

Genomic imprinting has been identified in therian (eutherian and marsupial) mammals but not in prototherian (monotreme) mammals. Imprinting has an important role in optimising pre-natal nutrition and growth, and most imprinted genes are expressed and imprinted in the placenta and developing fetus. In marsupials, however, the placental attachment is short-lived, and most growth and development occurs post-natally, supported by a changing milk composition tailor-made for each stage of development. Therefore there is a much greater demand on marsupial females during post-natal lactation than during pre-natal placentation, so there may be greater selection for genomic imprinting in the mammary gland than in the short-lived placenta. Recent studies in the tammar wallaby confirm the presence of genomic imprinting in nutrient-regulatory genes in the adult mammary gland. This suggests that imprinting may influence infant post-natal growth via the mammary gland as it does pre-natally via the placenta. Similarly, an increasing number of imprinted genes have been implicated in regulating feeding and nurturing behaviour in both the adult and the developing neonate/offspring in mice. Together these studies provide evidence that genomic imprinting is critical for regulating growth and subsequently the survival of offspring not only pre-natally but also post-natally.

show abstract

Section: The Evolution Of Imprinting In the Post-natal Mammalmentioning

confidence: 99%

Post-natal imprinting: evidence from marsupials

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Magel2 encodes a putative transcriptional regulator expressed predominately in the brain and especially during late developmental stages in the hypothalamus (Kozlov et al 2007). Magel2-deficient mice exhibit neonatal growth retardation, altered metabolism and increased adiposity, despite a reduction in food intake (Bischof et al 2007, Kozlov et al 2007. They have reduced numbers of orexin neurons and orexin levels in the lateral hypothalamus, suggesting a role for Magel2 in neuronal development.…”

Section: Studies Of Imprinted Gene Function In the Hypothalamusmentioning

confidence: 99%

Imprinted genes and hypothalamic function

Ivanova

Kelsey

2011

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Genomic imprinting is an important and enigmatic form of gene regulation in mammals in which one copy of a gene is silenced in a manner determined by its parental history. Imprinted genes range from those with constitutive monoallelic silencing to those, typically more remote from imprinting control regions, that display developmentally regulated, tissuespecific or partial monoallelic expression. This diversity may make these genes, and the processes they control, more or less sensitive to factors that modify or disrupt epigenetic marks. Imprinted genes have important functions in development and physiology, including major endocrine/neuroendocrine axes. Owing to is central role in coordinating growth, metabolism and reproduction, as well as evidence from genetic and knockout studies, the hypothalamus may be a focus for imprinted gene action. Are there unifying principles that explain why a gene should be imprinted? Conflict between parental genomes over limiting maternal resources, but also co-adaptation between mothers and offspring, have been invoked to explain the evolution of imprinting. Recent reports suggest there may be many more genes imprinted in the hypothalamus than hitherto expected, and it will be important for these new candidates to be validated and to determine whether they conform to current notions of how imprinting is regulated. In fully evaluating the role of imprinted genes in the hypothalamus, much work needs to be done to identify the specific neuronal populations in which particular genes are expressed, establish whether there are pathways in common and whether imprinted genes are involved in long-term programming of hypothalamic functions.

show abstract

“…It is localised to the PWS locus in humans and the syntenic region in mice, and is paternally expressed (Boccaccio et al, 1999). Deletion of Magel2 from the paternally inherited allele in mice phenocopies some aspects of PWS: the animals fail to thrive in the early postnatal period, but later experience catch-up growth and as adults have increased adiposity (Bischof et al, 2007). However, this energy imbalance is not caused by hyperphagia in the mutant mice because although they eat less, they have reduced energy expenditure.…”

Section: Prader-willi Syndrome Clustermentioning

confidence: 99%

Genomic imprinting, growth and maternal–fetal interactions

Cassidy

Charalambous

2018

Journal of Experimental Biology

View full text Add to dashboard Cite

In the 1980s, mouse nuclear transplantation experiments revealed that both male and female parental genomes are required for successful development to term (McGrath and Solter, 1983; Surani and Barton, 1983). This non-equivalence of parental genomes is because imprinted genes are predominantly expressed from only one parental chromosome. Uniparental inheritance of these genomic regions causes paediatric growth disorders such as Beckwith–Wiedemann and Silver–Russell syndromes (reviewed in Peters, 2014). More than 100 imprinted genes have now been discovered and the functions of many of these genes have been assessed in murine models. The first such genes described were the fetal growth factor insulin-like growth factor 2 (Igf2) and its inhibitor Igf2 receptor (Igf2r) (DeChiara et al., 1991; Lau et al., 1994; Wang et al., 1994). Since then, it has emerged that most imprinted genes modulate fetal growth and resource acquisition in a variety of ways. First, imprinted genes are required for the development of a functional placenta, the organ that mediates the exchange of nutrients between mother and fetus. Second, these genes act in an embryo-autonomous manner to affect the growth rate and organogenesis. Finally, imprinted genes can signal the nutritional status between mother and fetus, and can modulate levels of maternal care. Importantly, many imprinted genes have been shown to affect postnatal growth and energy homeostasis. Given that abnormal birthweight correlates with adverse adult metabolic health, including obesity and cardiovascular disease, it is crucial to understand how the modulation of this dosage-sensitive, epigenetically regulated class of genes can contribute to fetal and postnatal growth, with implications for lifelong health and disease.

show abstract

Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome

Cited by 179 publications

References 35 publications

Post-natal imprinting: evidence from marsupials

Post-natal imprinting: evidence from marsupials

Imprinted genes and hypothalamic function

Genomic imprinting, growth and maternal–fetal interactions

Contact Info

Product

Resources

About