Analysis Tools
mortality/aging
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• embryonic (E) and postnatal (P) lethality, ranging from E9.5 to P28
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• the survival of homozygous pups after 1 month is only 20% compared with wild-type
• paternal inheritance of the targeted allele seemed to be more critical than maternal transmission for the survival of offspring
• 30% of the males and just 10% of the females survived compared with wild-type littermates
• 89% male and 60% female embryos present compared with wild-type embryos at E10-E12.5 following heterozygous crosses
• in homozygous male with heterozygous female crosses, the ratio of homozygous pups is significantly skewed against females, with one female born for every three to four males
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growth/size/body
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• maldeveloped teeth
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• assymetric shortening and curving unilaterally of the nasal bones in adult mice
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short snout
(
J:166841
)
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• shortened snout at E18.5
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• reduced average body weight at 1-month and 9-month of age
• 25%-40% lower than that of wild type in males and 15% lower than that of wild type in females at 1-month of age
• 20% lower that of wild type in males and 7% lower that of wild type in females at 9-month of age
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• incompletely penetrant
• some have severely reduced body size in combination with a bilateral microphthalmic eye phenotype and exencephaly at E14.5
• some have slightly reduced body size at E18.5
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reproductive system
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• extensive apoptosis and reduced number of germ cells in 5-10% of the seminiferous tubules at 9-month of age
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• spermatogonia not only in the first basal layer, but also in the subbasal layers in several tubules at 12-month of age
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• extensive apoptosis and reduced number of germ cells in 5-10% of the seminiferous tubules at 9-month of age
• numerous apoptotic and degraded spermatocytes, spermatids, and round and elongating spermatids
• no apoptotic cells in spermatogonia and spermatocytes
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small testis
(
J:166841
)
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• smaller testis size at 12-month of age
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• reduced testis weight at 12-week and 12-month of age
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• decreased average litter size
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vision/eye
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• absent pupils and various degrees of eye malformations in adult mice
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• lens is either completely missing or clearly smaller and displaced in the eye field
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• lens fiber cells lose their ordered lamination pattern
• swollen and liquefied fibers as well as vacuoles throughout the lens
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• most often in the right eye (unilateral) in 18% of E11.5-E12.5 embryos and 9% of adult mice
• eye defects vary from unilateral to bilateral
• microphthalmia or anophthalmia, or unilateral microphthalmia in combination with unilateral anophthalmia
• affect the right eye more severely than the left eye
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• severe loss of organization in retinal cells
• the neural retina is dysplastic with inclusions of rods and cones surrounded by outer nuclear layer cells, forming rosettes in some areas
• thick layers of retinal pigment epithelium (RPE) cells, with RPE cells appearing inside the multi-layered neural retina in direct contact with the lens
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• degenerated retinal cells
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anophthalmia
(
J:166841
)
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• most often in the right eye (unilateral) in 18% of E11.5-E12.5 embryos and 9% of adult mice
• eye defects vary from unilateral to bilateral
• microphthalmia or anophthalmia, or unilateral microphthalmia in combination with unilateral anophthalmia
• affect the right eye more severely than the left eye
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nervous system
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• severe intracranial hemorrhage in some embryos at E12.5
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• neural tube defects (NTDs) in 10% of embryos at E10.5-E11.5
• disrupted closure in the midbrain-hindbrain region and upper spinal region
• frequently associated with head and facial malformations
• 50% of embryos with NTDs simultaneously displayed eye malformations
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exencephaly
(
J:166841
)
skeleton
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• bigger sutures in the skull at E18.5
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• reduced or missing ossification of the frontal bones
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• shortened frontal bones at E18.5
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• reduced or missing ossification of the interparietal bones
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• reduced or missing ossification of the parietal bones
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• maldeveloped teeth
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• upward curving of the lower jaws at E18.5
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• assymetric shortening and curving unilaterally of the nasal bones in adult mice
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• reduced ossification in the phalanges of the autopod of mutant newborns
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• reduced ossification in the metatarsals of the autopod of mutant newborns
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• delayed ossification and severe aberrant fusion of the sternal bands in newborn mice
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• delayed ossification of the sternal bands in newborn mice
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• reduced or missing ossification of the interparietal, parietal and frontal bones leading to bigger sutures in the skull at E18.5
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• reduced or missing ossification of the interparietal, parietal and frontal bones leading to bigger sutures in the skull at E18.5
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• reduced ossification in the phalanges and the metatarsals of the autopod of mutant newborns
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cardiovascular system
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• severe intracranial hemorrhage in some embryos at E12.5
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craniofacial
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• bigger sutures in the skull at E18.5
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• reduced or missing ossification of the frontal bones
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• shortened frontal bones at E18.5
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• reduced or missing ossification of the interparietal bones
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• reduced or missing ossification of the parietal bones
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• maldeveloped teeth
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• upward curving of the lower jaws at E18.5
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• assymetric shortening and curving unilaterally of the nasal bones in adult mice
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short snout
(
J:166841
)
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• shortened snout at E18.5
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limbs/digits/tail
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• reduced ossification in the phalanges of the autopod of mutant newborns
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• reduced ossification in the metatarsals of the autopod of mutant newborns
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embryo
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• neural tube defects (NTDs) in 10% of embryos at E10.5-E11.5
• disrupted closure in the midbrain-hindbrain region and upper spinal region
• frequently associated with head and facial malformations
• 50% of embryos with NTDs simultaneously displayed eye malformations
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endocrine/exocrine glands
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• spermatogonia not only in the first basal layer, but also in the subbasal layers in several tubules at 12-month of age
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• extensive apoptosis and reduced number of germ cells in 5-10% of the seminiferous tubules at 9-month of age
• numerous apoptotic and degraded spermatocytes, spermatids, and round and elongating spermatids
• no apoptotic cells in spermatogonia and spermatocytes
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small testis
(
J:166841
)
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• smaller testis size at 12-month of age
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• reduced testis weight at 12-week and 12-month of age
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cellular
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• extensive apoptosis and reduced number of germ cells in 5-10% of the seminiferous tubules at 9-month of age
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• pachytene spermatocytes exhibit upregulation of individual piRNAs compared with wild-type cells
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respiratory system
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• assymetric shortening and curving unilaterally of the nasal bones in adult mice
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