Math1-driven GFP expression in the developing nervous system of transgenic mice

Lumpkin, Ellen A.; Collisson, Tandi; Parab, Preeti; Omer-Abdalla, Adil; Haeberle, Henry; Chen, Ping; Doetzlhofer, Angelika; White, Patricia M.; Groves, Andrew K.; Segil, Neil; Johnson, Jane E.

doi:10.1016/s1567-133x(03)00089-9

Cited by 270 publications

(367 citation statements)

References 29 publications

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“…Within the vestibular and auditory sensory epithelia, we found cells of defined shape with filamentous actin-containing hair bundles that were immunopositive for the hair bundle marker espin (Roblin et al 2003;Zheng et al 2000). These hair cells displayed green fluorescence, indicative of the nGFP reporter that is expressed in the nuclei of the transgenic Math1/nGFP mouse line (Lumpkin et al 2003) used for our study. Nevertheless, at 10 days postmortem, the distribution of nGFP was typically no longer mainly nuclear (Fig.…”

Section: Morphology and Cell Survival In Postmortem Inner Ear Tissuesmentioning

confidence: 81%

“…Newborn (P1/P2) or 3-week-old (P21) Math-1/nuclear green fluorescence protein (nGFP) mice (Lumpkin et al 2003) were euthanatized by CO 2 overdose. To ensure death, we exposed the animals to 100% CO 2 for 2 h, which is more than twice the maximum time to death reported for newborn neonatal mice with this procedure (Pritchett et al 2005).…”

Section: Animalsmentioning

confidence: 99%

“…It has been shown previously that splitthickness skin grafts can be allografted up to 3 weeks after death if stored at 4-C (Rosenquist et al 1988), a fact that supports our results with surviving cells in the inner ear up to 15 days postmortem. More recently, stem and progenitor cells have been isolated from postmortem brain, spinal cord, and the retina (Laywell et al 1999;Mayer et al 2005;Palmer et al 2001;Roisen et al 2001). Generally, it appears that many stem cells survive for hours or even days after death, but no study thus far has systematically and quantitatively investigated the postmortem time course of the decrease in stem cell numbers and the specific potential of stem cells isolated at different postmortem time intervals.…”

Section: Stem Cells After Deathmentioning

confidence: 99%

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Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Senn

Oshima

Teo

et al. 2007

JARO

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Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

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Section: Morphology and Cell Survival In Postmortem Inner Ear Tissuesmentioning

confidence: 81%

Section: Animalsmentioning

confidence: 99%

Section: Stem Cells After Deathmentioning

confidence: 99%

See 1 more Smart Citation

Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Senn

Oshima

Teo

et al. 2007

JARO

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“…Three 6-week-old Atoh1-GFP mice 28 were injected with Cas9:GFP-targeting sgRNA:lipid complex, with the same concentration and volume for each component as used in injection into neonatal inner ear. Mice were anesthetized by intraperitoneal injection of combination of xylazine (10 mg/kg) and ketamine (100 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents

Gao

Tao

Lamas

et al. 2017

Nature

446

346

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Although genetic factors contribute to almost half of all deafness cases, treatment options for genetic deafness are limited1–5. We developed a genome editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9:guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated in vitro and in primary fibroblasts genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like 1) Beethoven (Bth) mouse model, even though the mutant Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9:guide RNA:lipid complexes targeting the Bth allele into the cochlea of neonatal Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response (ABR) thresholds in injected ears compared with uninjected ears or ears injected with complexes that target an unrelated gene. Enhanced acoustic reflex responses were observed among injected compared to uninjected Bth/+ animals. These findings suggest protein:RNA complex delivery of target gene-disrupting agents in vivo as a potential strategy for the treatment of some autosomal dominant hearing loss diseases.

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“…A hallmark of these pluripotent vestibular stem cells is their ability to form clonal, free-floating colonies, called spheres. Hair cell progenitors have also been derived from the early postnatal rat cochlea (Malgrange et al 2002;Zhai et al 2005). To evaluate whether regenerative capacity of vestibular and cochlear tissues correlates with the presence of stem cells, we isolated sphere-forming stem cells at various ages from postnatal day 1 to 4 months of age.…”

Section: Introductionmentioning

confidence: 99%

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

Oshima

Grimm

Corrales

et al. 2006

JARO

297

361

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The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.

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Math1-driven GFP expression in the developing nervous system of transgenic mice

Cited by 270 publications

References 29 publications

Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

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