Analysis Tools
mortality/aging
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• only ~15% of mice survive to adulthood but these become indistinguishable from wild-type controls
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• only a few homozygotes are obtained from heterozygous matings at 2-3 weeks of age; however, homozygotes are present at normal Mendelian ratios at E14.5-E15.5, indicating death in utero after E15 or within 2 weeks of birth
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• 50% of homozygotes die within 24 hours of birth
• however, homozygotes are present at normal Mendelian ratios at E18.5
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• only ~15% of homozygotes survive to P21
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hematopoietic system
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• E14.5 embryos exhibit a block in terminal erythroid differentiation
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• E14.5 Ter119+ cells express higher levels of TFRC (transferrin receptor, aka CD71) relative to heterozygous and wild-type Ter119+ cells, indicating that erythroid differentiation is compromised
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• E14.5 fetal liver displays significantly fewer terminally differentiating Ter119+ erythroblasts relative to those found in wild-type or heterozygous embryos
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behavior/neurological
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• P0 mice contain no gastric milk
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• P0 mice show great difficulty in attaching to the mothers nipple, as shown by a 3-fold increase in the latency of nipple attachment relative to wild-type controls
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• P0 mice show severe uncoordinated movements during nipple attachment, indicating loss of motor control
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growth/size/body
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• mice are significant smaller than wild-type controls at P10-P15
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• mice weigh significantly less than wild-type controls at P10-P15
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respiratory system
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• P0 mice exhibit occasional gasping
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nervous system
| N |
• mice surviving to adulthood exhibit no detectable motor neuron degeneration, as assessed by compound muscle action potential (CMAP), motor unit number estimation, motor unit size and electromyography score in the sciatic nerve of hind limbs at 2 years of age
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• at E18.5, phrenic nerve axons are thin and display only a few arbors with a significant reduction in secondary and tertiary axon branching, unlike in wild-type controls
• however, neither forelimb nor ophthalmic sensory neurons exhibit axon branching defects
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• at E18.5, phrenic nerve axons are thin and display only a few arbors with a significant reduction in secondary and tertiary axon branching, unlike in wild-type controls
• quantification of alpha-bungarotoxin puncta area over the diaphragm muscle area showed >50% reduction similar to the loss of axonal terminals, indicating reduced innervation and subsequent loss of acetylcholine receptor cluster formation
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• cultured hippocampal neurons, like P0 spinal cords, show elevated Fam107a (Drr1) mRNA levels and reduced neurite outgrowth relative to wild-type neurons
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• P0 mice exhibit a significant reduction of neuromuscular junction formation in the diaphragm, as revealed by staining with alpha-bungarotoxin (a marker for acetylcholine receptors)
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cellular
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• P0 spinal cords show an ~40% increase in the products for 5' junctions of 5.8S and 28S rRNAs, indicating reduced rRNA processing; however, mature levels of 18S, 5.8S, and 28S remain normal, suggesting a mild impairment of nucleolar function
• at P0, several stress response genes such as Fam107a (family with sequence similarity 107, also known as Drr1), which encodes an actin bundling protein and impedes neurite outgrowth, are significantly increased in the spinal cord
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• at E18.5, phrenic nerve axons are thin and display only a few arbors with a significant reduction in secondary and tertiary axon branching, unlike in wild-type controls
• however, neither forelimb nor ophthalmic sensory neurons exhibit axon branching defects
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muscle
| N |
• mice surviving to adulthood exhibit no visible pathological changes in skeletal muscle
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