Phenotypes associated with this allele

• Allele Symbol: Otx1^tm1Asim
• Allele Name: targeted mutation 1, Antonio Simeone
• Allele ID: MGI:2136272
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Otx1^tm1Asim/Otx1^tm1Asim	involves: 129P2/OlaHsd	MGI:3845660
hm2	Otx1^tm1Asim/Otx1^tm1Asim	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2175195
cx3	Otx1^tm1Asim/Otx1^tm1Asim Otx2^tm1Pas/Otx2^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3578521
cx4	Otx1^tm1Asim/Otx1^tm2(otd)Asim Otx2^tm1Pas/Otx2^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3845768

Genotype
MGI:3845660

hm1

• Allelic Composition: Otx1^tm1Asim/Otx1^tm1Asim
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

seizures ( J:52989 )

• mice exhibit prolonged seizures in the hippocampus and cortex

abnormal telencephalon development ( J:52989 )

• cell proliferation in the dorsal telencephalon is decreased compared to in Otx1^{tm3(OTX2)Asim} homozygotes

decreased brain size ( J:52989 )

• by 25% to 30%

decreased brain weight ( J:52989 )

• by 25% to 30%

abnormal cerebral cortex morphology ( J:52989 )

• the dorsal telencephalic cortex is reduced in thickness and cell number, especially in the temporal and perirhinal areas, compared to in wild-type mice

• cell layers of the cortex are disorganized in the temporal and perirhinal areas where the sulcus rhinalis is hardly recognizable

mortality/aging

premature death ( J:47322 )

• 80% lethality

vision/eye

absent lacrimal glands ( J:52989 )

absent ciliary process ( J:52989 )

• the ciliary process is absent

hearing/vestibular/ear

abnormal inner ear morphology ( J:52989 )

absent lateral semicircular canal ( J:52989 )

behavior/neurological

seizures ( J:52989 )

• mice exhibit prolonged seizures in the hippocampus and cortex

endocrine/exocrine glands

absent lacrimal glands ( J:52989 )

absent Harderian gland ( J:52989 )

Genotype
MGI:2175195

hm2

• Allelic Composition: Otx1^tm1Asim/Otx1^tm1Asim
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

growth/size/body

decreased body weight ( J:47322 )

• normal body weight and size at birth

• peak reduction of body weight around 30 days of age

• body weight returned to normal around 100 days (~3.5 months) of age

postnatal growth retardation ( J:47322 )

• reduction of growth rate beginning by the first week of age

• growth rate returned to normal by fourth month of age

behavior/neurological

convulsive seizures ( J:35640 )

• characteristic of generalized seizures displaying upper extremety clonus, rearing and falling

• episodes last ~ 60 seconds with a full recovery

• spikes recorded in the hippocampus and cortex

nonconvulsive seizures ( J:35640 )

• characteristic of focal seizures displaying automatisms of head bobbing and teeth chattering

• mice either recovered from these episodes or the seizures generalized into convulsive seizures

• spikes recorded in the hippocampus

hearing/vestibular/ear

absent semicircular canals ( J:35640 )

• absence of lateral semicircular duct

homeostasis/metabolism

decreased circulating testosterone level ( J:47322 )

• markedly reduced at 30 days of age

• normal levels restored by 4 months of age

vision/eye

absent lacrimal glands ( J:35640 )

abnormal iris morphology ( J:35640 )

• reduction in size

• absence of cilliary process

mortality/aging

premature death ( J:47322 )

• 25% lethaltiy, mixed C57BL/6 and DBA/2 F1 background

nervous system

convulsive seizures ( J:35640 )

• characteristic of generalized seizures displaying upper extremety clonus, rearing and falling

• episodes last ~ 60 seconds with a full recovery

• spikes recorded in the hippocampus and cortex

nonconvulsive seizures ( J:35640 )

• characteristic of focal seizures displaying automatisms of head bobbing and teeth chattering

• mice either recovered from these episodes or the seizures generalized into convulsive seizures

• spikes recorded in the hippocampus

abnormal pituitary secretion ( J:47322 )

• normal pituitary cell number, indicating defect in hormone synthesis

increased cerebellar foliation ( J:35640 )

• 80% of mice showed an additional lobule and 15% showed an additional duplication of the rostral end of the declivus

decreased brain weight ( J:47322 )

• 20-25% reduction in weight, with no recovery

abnormal midbrain morphology ( J:35640 )

• an additional structure was detected between the superior and inferior colliculi in ~20% of mice

increased inferior colliculus size ( J:35640 )

increased superior colliculus size ( J:35640 )

abnormal cerebral cortex morphology ( J:35640 )

• reduction in the weight of dorsal telencephalic cortex

reproductive system

abnormal ovarian folliculogenesis ( J:47322 )

♀ • absence of advanced differentiating follicles at 30 days of age

♀ • advanced differentiating follicles and corpora lutea were observed by 4 months of age

small ovary ( J:47322 )

♀

abnormal seminiferous tubule morphology ( J:47322 )

♂ • normal histology at 1, 5, and 10 days of age

♂ • no open lumen observed at 20 days of age

♂ • strongly or completely depleted of secondary spermatocytes at 30 days of age

small testis ( J:47322 )

♂ • maximal reduced size at 30 days of age

♂ • normal size observed at both 10 days and 4 months of age

arrest of spermatogenesis ( J:47322 )

♂ • differentiation of spermatocytes ceased until gonadotropic hormone levels were restored

delayed fertility ( J:47322 )

endocrine/exocrine glands

absent lacrimal glands ( J:35640 )

absent Harderian gland ( J:35640 )

abnormal ovarian folliculogenesis ( J:47322 )

♀ • absence of advanced differentiating follicles at 30 days of age

♀ • advanced differentiating follicles and corpora lutea were observed by 4 months of age

small ovary ( J:47322 )

♀

abnormal seminiferous tubule morphology ( J:47322 )

♂ • normal histology at 1, 5, and 10 days of age

♂ • no open lumen observed at 20 days of age

♂ • strongly or completely depleted of secondary spermatocytes at 30 days of age

small testis ( J:47322 )

♂ • maximal reduced size at 30 days of age

♂ • normal size observed at both 10 days and 4 months of age

abnormal pituitary secretion ( J:47322 )

• normal pituitary cell number, indicating defect in hormone synthesis

Genotype
MGI:3578521

cx3

• Allelic Composition: Otx1^tm1Asim/Otx1^tm1Asim; Otx2^tm1Pas/Otx2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

nervous system

abnormal neuron morphology ( J:88192 )

abnormal dopaminergic neuron morphology ( J:88192 )

• dopaminergic domain shifted rostrally into the diencephalon at E12.5 and E15.5

abnormal serotonergic neuron morphology ( J:88192 )

• serotonergic neuron domain expands rostrally to the diencephalon at E12.5 and E15.5

Genotype
MGI:3845768

cx4

• Allelic Composition: Otx1^tm1Asim/Otx1^tm2(otd)Asim; Otx2^tm1Pas/Otx2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

perinatal lethality, complete penetrance ( J:47899 )

• mice die at birth

nervous system

abnormal brain morphology ( J:47899 )

• mice exhibit abnormal brain morphology

• however, the dorsal thalamus, Ammon's horn, and pretectum absent in Otx1^tm1Asim/Otx1^tm1Asim Otx2^tm1Pas/Otx2⁺ are restored

abnormal midbrain morphology ( J:47899 )

• mice exhibit abnormal mesencephalic morphology with a reduction in thickness of the alar region compared to in wild-type mice

abnormal cerebellum morphology ( J:47899 )