Pre-weaning Sensorial and Motor Development in Mice Transpolygenic for the Critical Region of Trisomy 21

Roubertoux, Pierre L.; Bichler, Zoë; Pinoteau, Walter; Jamon, Marc; Sérégaza, Zohra; Smith, Desmond J.; Rubin, Edward M.; Migliore‐Samour, Danièle

doi:10.1007/s10519-006-9055-x

Cited by 17 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tests performed were: righting reflex, negative geotaxis, level screen test, cliff aversion, and auditory startle, described in detail below (Heyser 2004; Roubertoux et al 2006; Scattoni et al 2008). Pups were weighed prior to each testing period and were reunited with their mother immediately after testing.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

et al. 2012

View full text Add to dashboard Cite

Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders – such as Tuberous Sclerosis Complex – can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders.

show abstract

Section: Methodsmentioning

confidence: 99%

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Our data show both expression and functionality of KCNJ6 in transgenic mouse lines Tg67 ϩ/ϩ and Tg84 ϩ/ϩ carrying YAC 285E6. Formerly restricted to CBR and PCP4 boundaries, this YAC has since been more precisely mapped to a single gene, namely KCNJ6 (7,33). According to Smith et al (36), the Tg67 ϩ/Ϫ line has integrated one copy of the YAC.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, those of Smith et al (36) cover the DSCR using four contiguous yeast artificial chromosomes (YAC). Mouse lines bearing the YAC 152F7, 230E8, and 141G6 have affected brain weight, neuron size and density, and/or behavioral responses (7,10,33,37). The fourth, YAC 285E6, includes the large KCNJ6 gene (7,33).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21

Lignon

Bichler

Hivert

et al. 2008

Physiological Genomics

Self Cite

View full text Add to dashboard Cite

Congenital heart defects (CHD) are common in Down syndrome (DS, trisomy 21). Recently, cardiac sympathetic-parasympathetic imbalance has also been documented in DS adults free of any CHD. The KCNJ6 gene located on human chromosome 21 encodes for the Kir3.2/GIRK2 protein subunits of G protein-regulated K(+) (K(G)) channels and could contribute to this altered cardiac regulation. To elucidate the role of its overexpression, we used homozygous transgenic (Tg(+/+)) mice carrying copies of human KCNJ6. These mice showed human Kir3.2 mRNA expression in the heart and a 2.5-fold increased translation in the atria. Phenotypic alterations were assessed by recording electrocardiogram of urethane anesthetized mice. Chronotropic responses to direct (carbachol) and indirect (methoxamine) muscarinic stimulation were enhanced in Tg(+/+) mice with respect to wild-type (WT) mice. Alternating periods of slow and fast rhythm induced by CCPA (2-chloro-N-cyclopentyl-adenosine) were amplified in Tg(+/+) mice, resulting in a reduced negative chronotropic effect. These drugs reduced the atrial P wave amplitude and area. P wave variations induced by methoxamine and CCPA were respectively increased and reduced in the Tg(+/+) mice, while PR interval and ventricular wave showed no difference between Tg(+/+) and WT. These results indicate that Tg(+/+) mice incorporating the human KCNJ6 exhibit altered Kir3.2 expression and responses to drugs that would activate K(G) channels. Moreover, these altered expression and responses are limited to sino-atrial node and atria that normally express large amounts of K(G) channels. These data suggest that KCNJ6 could play an important role in altered cardiac regulation in DS patients.

show abstract

“…Unlike plasmid pronuclear injection, large genomic transgenes are more likely to produce copy number dependent transgene expression that is independent of positional effects and better recapitulate endogenous gene expression patterns (Chandler et al, 2007, Giraldo andMontoliu, 2001). YAC models have been developed and analysed to understand the contribution of some DS genes, including DYRK1A, to cognitive function and other features (Guedj et al, 2009, Sebrie et al, 2008, Rachidi et al, 2007, Roubertoux et al, 2006, Branchi et al, 2004, Smith et al, 1995. The use of BAC transgenesis to model DS is technically complex and time-consuming.…”

Section: Ii21 the Early Age Of Transgenic Tg Yac And Bac: Ds Mousementioning

confidence: 99%

Modeling Down syndrome in animals from the early stage to the 4.0 models and next

Moreno

Brault

Birling

et al. 2020

Progress in Brain Research

View full text Add to dashboard Cite

Short Abstract (<200 words)The genotype-phenotype relationship and the physiopathology of Down Syndrome (DS) have been explored in the last twenty years with more and more relevant mouse models. From the early age of transgenesis to the new CRISPR/CAS9-derived chromosomal engineering and the transchromosomic technologies, mouse models have been key to identify homologous genes or entire regions homologous to the human chromosome 21 that are necessary or sufficient to induce DS features, to investigate the complexity of the genetic interactions that are involved in DS and to explore therapeutic strategies. In this review we report the new developments made, how genomic data and new genetic tools have deeply changed our way of making models, extended our panel of animal models, and increased our understanding of the neurobiology of the disease. But even if we have made an incredible progress which promises to make DS a curable condition, we are facing new research challenges to nurture our knowledge of DS pathophysiology as a neurodevelopmental disorder with many comorbidities during ageing. Keyword listGenome, animal models, transgenesis, chromosomal engineering, transchromosomic, behaviour and cognition, neurobiology of disease.

show abstract

Pre-weaning Sensorial and Motor Development in Mice Transpolygenic for the Critical Region of Trisomy 21

Cited by 17 publications

References 41 publications

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21

Modeling Down syndrome in animals from the early stage to the 4.0 models and next

Contact Info

Product

Resources

About