Analysis Tools
mortality/aging
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• although homozygous pups are born at normal Mendelian ratios, about half (48%) of them die within 24-48 hrs after birth
• 70% of neonatal death is due to a breathing problem
• Background Sensitivity: homozygotes of a mixed genetic background show no evidence of neonatal lethality
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growth/size/body
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• homozygotes surviving the initial 48 hrs are frequently smaller than wild-type pups
• however, gross development is otherwise normal
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respiratory system
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• lungs frequently show no sign of breathing
• however, tracheal cartilage appears normal
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behavior/neurological
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• pups that die within 24 hrs of birth do not have milk in their stomachs
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nervous system
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• at E14.5, percentage of BrdU-positive DCT labelling melanoblasts following a 24-hr BrdU pulse is significantly reduced relative to wild-type controls
• fewer phospho-histone H3 (pH3, mitosis marker)-positive DCT labelling melanoblasts are observed at E14.5
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• the lateral ventricle is larger than normal
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• the posterior part of the anterior commissure is missing with 100% penetrance (8 of 8 brains)
• however, the anterior region of the anterior commissure appears normal
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• in vitro, DRGs are able to extend neurons upon NGF treatment, indicating normal neurite extension; however, growth cones are smaller and exhibit fewer and shorter filopodia than wild-type controls
• neurite outgrowth of explanted DRGs in collagen gels is normal
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• in vitro, axons of DRG neurons appear less straight and frequently thinner than those in wild-type controls
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immune system
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• dendritic cells exhibit less membrane protrusion activity compared with wild-type cells
• dendritic cells are more spread and thinner with fewer membrane protrusion compared with wild-type cells
• dendritic cells fail to disassemble podosomes upon maturation unlike wild-type cells
• however, forced expression of Fscn1 restores podosome disassembly
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• chemotaxis towards CCL19 is impaired compared with wild-type cells
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• Langerhans cells exhibit reduced migration into lymph nodes compared with wild-type cells
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pigmentation
belly spot
(
J:197025
)
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• mice exhibit a white patch near the midline of the abdomen, varying from a few white hairs or a thin straight white line (63%) to a large diversely shaped white patch covering 5-20% of the abdomen (37%)
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• reduced pigmentation in the toes
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• reduced pigmentation in the tail
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• absence of melanocytes in the white patch of abdominal skin at P14 (hair follicle in anagen stage)
• however, the black dorsal skin shows normal melanocyte distribution
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integument
belly spot
(
J:197025
)
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• mice exhibit a white patch near the midline of the abdomen, varying from a few white hairs or a thin straight white line (63%) to a large diversely shaped white patch covering 5-20% of the abdomen (37%)
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• reduced pigmentation in the toes
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• reduced pigmentation in the tail
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embryo
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• at E14.5, percentage of BrdU-positive DCT labelling melanoblasts following a 24-hr BrdU pulse is significantly reduced relative to wild-type controls
• fewer phospho-histone H3 (pH3, mitosis marker)-positive DCT labelling melanoblasts are observed at E14.5
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cellular
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• at E14.5, percentage of nuclear cyclin D1-positive DCT labelling melanoblasts is significantly reduced relative to wild-type controls, indicating a delay in melanoblast cell cycle progression
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• chemotaxis towards CCL19 is impaired compared with wild-type cells
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• although cultured embryonic fibroblasts are able to assemble filopodia, live cell image analyses revealed that filopodia are significantly fewer, shorter, and short-lived, indicating reduced stability of filopodia in fibroblasts
• however, extension and retraction rates of filopodia are not significantly altered and wound healing is normal
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limbs/digits/tail
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• reduced pigmentation in the toes
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• reduced pigmentation in the tail
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hematopoietic system
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• chemotaxis towards CCL19 is impaired compared with wild-type cells
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