Measuring Preweaning Sensorial and Motor Development in the Mouse

Roubertoux, Pierre L.; Ghata, Adeline; Carlier, Michèle

doi:10.1002/cpmo.41

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…To determine whether sensory acquisitions were normal in the heterozygous knock‐in mice, using a protocol we recently developed, 11 15 traits featuring the sensory and motor development from P0 to P15 were measured. We considered the day of appearance of a pattern of adult response in the pup (righting, grasping, cliff avoidance, paw placing, geotaxis, auditory and visual onset, hindlimbs crossed extension, and rooting response).…”

Section: Resultsmentioning

confidence: 99%

A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

et al. 2020

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractObjective: Early onset epileptic encephalopathy with suppression-burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage-dependent potassium channel subunit, leading to so-called KCNQ2related epileptic encephalopathy (KCNQ2-REE). To study the pathophysiology of KCNQ2-REE in detail and to provide a relevant preclinical model, we generated and described a knock-in mouse model carrying the recurrent p.(Thr274Met) variant. Methods: We introduced the p.(Thr274Met) variant by homologous recombination in embryonic stem cells, injected into C57Bl/6N blastocysts and implanted in pseudopregnant mice. Mice were then bred with 129Sv Cre-deleter to generate heterozygous mice carrying the p.(Thr274Met), and animals were maintained on the 129Sv genetic background. We studied the development of this new model and performed in vivo electroencephalographic (EEG) recordings, neuroanatomical studies at different time points, and multiple behavioral tests. Results: The Kcnq2 Thr274Met/+ mice are viable and display generalized spontaneous seizures first observed between postnatal day 20 (P20) and P30. In vivo EEG recordings show that the paroxysmal events observed macroscopically are epileptic seizures. The brain of the Kcnq2 Thr274Met/+ animals does not display major structural defects, similar to humans, and their body weight is normal. Kcnq2 Thr274Met/+ mice have a reduced life span, with a peak of unexpected death occurring for 25% of the animals by 3 months of age. Epileptic seizures were generally not observed when animals grew older. Behavioral characterization reveals important deficits in spatial learning and memory in adults but no gross abnormality during early neurosensory development. | 869 MILH et aL.

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Section: Resultsmentioning

confidence: 99%

A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

et al. 2020

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“…Neurological examination of pre-weaned mice: A battery of neurodevelopmental tests for preweaned mice was developed in accordance with existing protocols(61)(62)(63)(64). Mice were assessed for achievement of bilateral eye opening, starting on DOL 11, hearing onset starting onDOL 11, …”

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confidence: 99%

Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome

Zhao¹,

Tassew²,

Lee³

et al. 2021

JCI Insight

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Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by inactivating mutations in SGPL1, which is required for the final step of sphingolipid metabolism. SPLIS features include steroid-resistant nephrotic syndrome (SRNS) and impairment of neurological, endocrine, and hematopoietic systems. Many affected individuals die within the first two years. No targeted therapy for SPLIS is available. We hypothesized that SGPL1 gene replacement would address the root cause of SPLIS, thereby serving as a universal treatment for the condition. As proof of concept, we evaluated the efficacy of adeno-associated virus 9-mediated transfer of human SGPL1 (AAV-SPL) given to newborn Sgpl1 KO mice that model SPLIS and die in the first weeks of life. Treatment dramatically prolonged survival and prevented nephrosis, neurodevelopmental delay, anemia, and hypercholesterolemia. STAT3 pathway activation and elevated pro-inflammatory and pro-fibrogenic cytokines observed in KO kidneys were attenuated by treatment. Plasma and tissue sphingolipids were reduced in treated compared to untreated KO pups. SGPL1 expression and activity were measurable for at least 40 weeks. In summary, early AAV-SPL treatment prevents nephrosis, lipidosis and neurological impairment in a mouse model of SPLIS. Our results suggest that SGPL1 gene replacement holds promise as a durable and universal targeted treatment for SPLIS.

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“…Visual, auditory and olfactory integrity is required to ensure the validity of the behavioral data. These sensorial capacities were tested according to previously described protocols 3,10,12,80 .…”

Section: Assessment Of Sensory Functionmentioning

confidence: 99%

TargetedTshz3deletion in corticostriatal circuit components segregates core autistic behaviors

Caubit

Gubellini

Roubertoux

et al. 2021

Preprint

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We previously linked TSHZ3 haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatal Tshz3 deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. We show that in the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABA interneurons, while not in cholinergic interneurons or glial cells. TSHZ3-expressing cells, which are predominantly SCINs in the striatum, represent a low proportion of neurons in the ascending cholinergic projection system. We then characterized two new conditional knockout (cKO) models generated by crossing Tshz3flox/flox with Emx1-Cre (Emx1-cKO) or Chat-Cre (Chat-cKO) mice to decipher the respective role of CPNs and SCINs. Emx1-cKO mice show altered excitatory synaptic transmission onto CPNs and plasticity at corticostriatal synapses, with neither cortical neuron loss nor impaired layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior. Chat-cKO mice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.

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Measuring Preweaning Sensorial and Motor Development in the Mouse

Cited by 11 publications

References 33 publications

A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome

TargetedTshz3deletion in corticostriatal circuit components segregates core autistic behaviors

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