Pathology of the Developing Mouse from Conception to Weaning

Bolon, Brad; Carreira, Vinicius

doi:10.1201/b18160-20

Cited by 6 publications

(7 citation statements)

References 419 publications

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“…After hindbrain sections were evaluated initially, 4-μm-thick step sections were acquired every 40 μm until 30-step sections had been harvested. The sectioning protocol was designed to evaluate major brainstem nuclei associated with control of respiration and facial movements, which have been linked to early neonatal death 38 . The positions of all three nuclei were approximated using landmarks defined in a well-recognized neuroanatomic atlas 39 .…”

Section: Methodsmentioning

confidence: 99%

MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration

et al. 2016

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Mitochondrial Ca2+ uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for tissue repair after injury. MICU1 knockout is perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration after partial hepatectomy as a physiological stress response model. Upon MICU1 loss, early priming is unaffected, but the pro-inflammatory phase does not resolve and liver regeneration fails, with impaired cell cycle entry and extensive necrosis. Ca2+ overload-induced mitochondrial permeability transition pore (PTP) opening is accelerated in MICU1-deficient hepatocytes. PTP inhibition prevents necrosis and rescues regeneration. Thus, our study identifies an unanticipated dependence of liver regeneration on MICU1 and highlights the importance of regulating MCU under stress conditions when the risk of Ca2+ overload is elevated.

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Section: Methodsmentioning

confidence: 99%

MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration

et al. 2016

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“…Mice were euthanized on PND7 and on PND21 (after recovery in room air) as most of postnatal lung development in mice is completed by this age. In mice, the alveolar stage extends from PND5 to PND28-30 (5,19,74). PND7 was an intermediate time point for alveolar development in mice, when we analyzed markers of angiogenesis, inflammatory cytokine expression, and the NF-B pathway mediators.…”

Section: Animalsmentioning

confidence: 99%

Sex-specific differences in neonatal hyperoxic lung injury

Lingappan

Jiang

Wang

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

103

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Male sex is considered an independent predictor for the development of bronchopulmonary dysplasia (BPD) after adjusting for other confounders. BPD is characterized by an arrest in lung development with marked impairment of alveolar septation and vascular development. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. In this investigation, we tested the hypothesis that male neonatal mice will be more susceptible to hyperoxic lung injury and will display larger arrest in lung alveolarization. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia [95% FiO2, postnatal day (PND) 1-5] and euthanized on PND 7 and 21. Extent of alveolarization, pulmonary vascularization, inflammation, and modulation of the NF-κB pathway were determined and compared with room air controls. Macrophage and neutrophil infiltration was significantly increased in hyperoxia-exposed animals but was increased to a larger extent in males compared with females. Lung morphometry showed a higher mean linear intercept (MLI) and a lower radial alveolar count (RAC) and therefore greater arrest in lung development in male mice. This was accompanied by a significant decrease in the expression of markers of angiogenesis (PECAM1 and VEGFR2) in males after hyperoxia exposure compared with females. Interestingly, female mice showed increased activation of the NF-κB pathway in the lungs compared with males. These results support the hypothesis that sex plays a crucial role in hyperoxia-mediated lung injury in this model. Elucidation of the sex-specific molecular mechanisms may aid in the development of novel individualized therapies to prevent/treat BPD.

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“…Some proteins may be indispensable, leading to lethality when the protein is absent, with other proteins contributing to adaptations helpful during stress, but otherwise providing functions replaceable by other proteins (Turgeon and Meloche 2009;Bolon 2015). During development, these influences also likely wax and wane leading to critical times for that protein to function (Papaioannou and Behringer 2012;Bolon and Carreira 2015;Bolon and Ward 2015). The presence of the BK channel protein in many cells types (Contreras et al 2013) creates the possibility for numerous points of altered function when this protein is absent, as illustrated both overtly and covertly in BK KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…The non‐Mendelian distribution of births (Table B, Fig. ) does not allow a determination of which developmental stage presents the disadvantage to particular pups; that definition will require a careful examination of fetuses at specified points of gestation together with measurement of placental blood perfusion (Papaioannou and Behringer ; Raz et al ; Bolon and Carreira ). Attention also would need to be given to the position of female fetuses relative to male fetuses because majority male litters exhibited the largest disadvantage (Fig.…”

Section: Discussionmentioning

confidence: 99%

Survival and growth of C57BL/6J mice lacking the BK channel,Kcnma1: lower adult body weight occurs together with higher body fat

et al. 2017

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Big conductance potassium (BK) channels contribute to K+ flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BKKO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0–P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20‐month period of building construction compared with the quiescent period after cessation of construction. Births during construction were not consistent with Mendelian predictions indicating the likelihood of a specific disadvantage induced by this environmental stressor. Later BKKO pup deaths (~P13) also were more numerous than Mendelian expectations. After weaning, weight gain was slower for BKKO mice compared with wild‐type littermates: 5 g less for male BKKO mice and 4 g less for female BKKO mice. Body composition determined by quantitative magnetic resonance indicated a higher fat proportion for wild‐type female mice compared with males, as well as a higher hydration ratio. Both male and female BKKO mice showed higher fat proportions than wild‐type, with female BKKO mice exhibiting greater variation. Together, these results indicate that BKKO mice suffered disadvantages that lead to prenatal and perinatal death. A metabolic difference likely related to glucose handling led to the smaller body size and distinct composition for BKKO mice, suggesting a diversion of energy supplies from growth to fat storage.

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Pathology of the Developing Mouse from Conception to Weaning

Cited by 6 publications

References 419 publications

MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration

MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration

Sex-specific differences in neonatal hyperoxic lung injury

Survival and growth of C57BL/6J mice lacking the BK channel,Kcnma1: lower adult body weight occurs together with higher body fat

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