Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone

Declercq, Jeroen; Brouwers, Bas; Pruniau, Vincent P. E. G.; Stijnen, Pieter; Faudeur, Geoffroy de; Tuand, Krizia; Meulemans, Sandra; Serneels, Lutgarde; Schraenen, Anica; Schuit, Frans; Creemers, John W.M.

doi:10.1371/journal.pone.0135502

Cited by 68 publications

(68 citation statements)

References 38 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7A). This weight gain developed despite known metabolic effects of Nes-Cre, which causes reduced body size (51). Thus, we conclude that Fgf13 in neurons contributes to the regulation of obesity.…”

Section: Fgf13 Heterozygous Knockout Decreases Sympathetic Drive To Batmentioning

confidence: 72%

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

et al. 2019

View full text Add to dashboard Cite

Fibroblast growth factor (FGF)13, a nonsecreted, X‐linked, FGF homologous factor, is differentially expressed in adipocytes in response to diet, yet Fgf13′s role in metabolism has not been explored. Heterozygous Fgf13 knockouts fed normal chow and housed at 22°C showed hyperactivity accompanying reduced core temperature and obesity when housed at 30°C. Those heterozygous knockouts showed defects in thermogenesis even at 30°C and an inability to protect core temperature. Surprisingly, we detected trivial FGF13 in adipose of wild‐type mice fed normal chow and no obesity in adipose‐specific heterozygous knockouts housed at 30°C, and we detected an intact brown fat response through exogenous β3 agonist stimulation, suggesting a defect in sympathetic drive to brown adipose tissue. In contrast, hypothalamic‐specific ablation of Fgf13 recapitulated weight gain at 30°C. Norepinephrine turnover in brown fat was reduced at both housing temperatures. Thus, our data suggest that impaired CNS regulation of sympathetic activation of brown fat underlies obesity and thermogenesis in Fgf13 heterozygous knockouts fed normal chow.—Sinden, D. S., Holman, C. D., Bare, C. J., Sun, X., Gade, A. R., Cohen, D. E., Pitt, G. S. Knockout of the X‐linked Fgf13 in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity. FASEB J. 33, 11579–11594 (2019). http://www.fasebj.org

show abstract

Section: Fgf13 Heterozygous Knockout Decreases Sympathetic Drive To Batmentioning

confidence: 72%

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It is worth mentioning that brain‐specific STAT5 KO mice exhibit reduced food intake during lactation, leading to decreased milk production and offspring growth . Furthermore, the Nestin‐Cre allele used to drive STAT5 deletion in the brain can cause metabolic and behavioural problems . Thus, the data obtained with brain‐specific STAT5 KO mice should be interpreted with caution because these confounding factors may have affected MCH expression in the mPOA.…”

Section: Discussionmentioning

confidence: 99%

Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

Teixeira

Wasinski

Lima

et al. 2019

J Neuroendocrinology

View full text Add to dashboard Cite

Neurones expressing the melanin‐concentrating hormone (MCH) can be found in the medial preoptic area (mPOA) and ventral aspects of the periventricular preoptic nucleus of rats by mid‐to‐late lactation and this expression disappears after weaning. The transitory expression of MCH in the preoptic area suggests a role for these neurones in the control of the end of lactation. However, the neurochemical identity of mPOA MCH neurones and the regulatory factors that control the transient MCH expression remain largely unknown, especially in the mouse. In the present study, we showed that mice also present the transitory expression of MCH in the mPOA at late lactation. mPOA MCH cells did not colocalise significantly with markers of GABAergic (VGAT), glutamatergic (VGLUT2 and VGLUT3) or dopaminergic (tyrosine hydroxylase) neurones. mPOA MCH cells also did not express Kiss1 or oxytocin. By contrast, approximately 70% and 90% of mPOA MCH neurones colocalised with oestrogen receptor α and prolactin‐induced phosphorylated signal transducer and activator of transcription 5 (STAT5), respectively. Finally, we demonstrated that the number of MCH neurones in the mPOA is significantly higher in females during the first lactation, compared to mice on the second lactation or pregnant mice during the first lactation or brain‐specific STAT5 knockout mice during the first lactation. In summary, our findings indicate that MCH neurones in the mPOA of lactating mice are sensitive to oestrogens and prolactin. Thus, mPOA MCH expression is possibly influenced by hormonal variations. Furthermore, the STAT5 signalling pathway is likely involved in the regulation of MCH expression in the mPOA of lactating mice.

show abstract

“…Even commonly used Cre driver lines, however, can have unexpected Cre activity patterns or show complicating phenotypes (Harno et al, 2013; Heffner et al, 2012; Schmidt-supprian and Rajewsky, 2007). For example, a Nestin-Cre mouse line ( Tg(Nes-cre)1Kln ), is one of the most commonly used Cre driver lines in the neuroscience field, but reports have revealed unexpected Cre expression in many tissues outside the central nervous system and a significant metabolic and behavioral phenotype in Nestin-Cre mice (Declercq et al., 2015; Giusti et al, 2014; Harno et al, 2013). These factors greatly complicate the interpretation of the derived phenotypes, and reduce the utility of this approach.…”

Section: Introductionmentioning

confidence: 99%

Generation and analysis of an improved Foxg1-IRES-Cre driver mouse line

Kawaguchi

Sahara

Zembrzycki

et al. 2016

Developmental Biology

View full text Add to dashboard Cite

Foxg1 expression is highly restricted to the telencephalon and other head structures in the early embryo. This expression pattern has been exploited to generate conditional knockout mice, based on a widely used Foxg1-Cre knock-in line (Foxg1tm1(cre)Skm), in which the Foxg1 coding region was replaced by the Cre gene. The utility of this line, however, is severely hampered for two reasons: (1) Foxg1-Cre mice display ectopic and unpredictable Cre activity, and (2) Foxg1 haploinsufficiency can produce neurodevelopmental phenotypes. To overcome these issues, we have generated a new Foxg1-IRES-Cre knock-in mouse line, in which an IRES-Cre cassette was inserted in the 3′UTR of Foxg1 locus, thus preserving the endogenous Foxg1 coding region and un-translated gene regulatory sequences in the 3′UTR, including recently discovered microRNA targeting sites. We further demonstrate that the new Foxg1-IRES-Cre line displays consistent Cre activity patterns that recapitulated the endogenous Foxg1 expression at embryonic and postnatal stages without causing defects in cortical development. We conclude that the new Foxg1-IRES-Cre mouse line is a unique and advanced tool for studying genes involved in the development of the telencephalon and other Foxg1-expressing regions starting from early embryonic stages.

show abstract

Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone

Cited by 68 publications

References 38 publications

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

Generation and analysis of an improved Foxg1-IRES-Cre driver mouse line

Contact Info

Product

Resources

About