Phenotypes associated with this allele

• Allele Symbol: Dyrk1a^tm1Mla
• Allele Name: targeted mutation 1, Maria L Arbones
• Allele ID: MGI:2386937
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dyrk1a^tm1Mla/Dyrk1a^tm1Mla	involves: 129P2/OlaHsd * C57BL/6	MGI:3613563
ht2	Dyrk1a^tm1Mla/Dyrk1a^+	involves: 129P2/OlaHsd	MGI:5430594
ht3	Dyrk1a^tm1Mla/Dyrk1a^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3613564

Genotype
MGI:3613563

hm1

• Allelic Composition: Dyrk1a^tm1Mla/Dyrk1a^tm1Mla
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:78597 )

• homozygous mutant embryos die between E10.5 and E13.5, with only 20% surviving at E13.5

growth/size/body

embryonic growth retardation ( J:78597 )

• at E9.5, E10.5, and E11.5, homozygotes display significant developmental structural delays in the heart, liver primordium, branchial arches, and brain vesicles

decreased embryo size ( J:78597 )

• at E9.5, E10.5, and E11.5, mutant embryos exhibit a 1/3 to 1/2 size reduction relative to wild-type embryos

embryo

embryonic growth retardation ( J:78597 )

• at E9.5, E10.5, and E11.5, homozygotes display significant developmental structural delays in the heart, liver primordium, branchial arches, and brain vesicles

decreased embryo size ( J:78597 )

• at E9.5, E10.5, and E11.5, mutant embryos exhibit a 1/3 to 1/2 size reduction relative to wild-type embryos

nervous system

abnormal nervous system development ( J:78597 )

• immunohistochemistry with an anti-beta-tubulin antibody, which specifically stains differentiating neuronal cells, revealed a reduction in the number of immunoreactive postmitotic neurons, indicating either defective neuroblast proliferation or delayed maturation of the nervous system

Genotype
MGI:5430594

ht2

• Allelic Composition: Dyrk1a^tm1Mla/Dyrk1a⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal brain size ( J:182294 )

• brains show shorter dorso-ventral length

abnormal thalamus morphology ( J:182294 )

• decrease in ventral posterolateral and ventral posteromedial thalamic nuclei volume (76% of control)

abnormal dentate gyrus morphology ( J:182294 )

• reduction in dentate gyrus volume (53% of control)

decreased hippocampus volume ( J:182294 )

• reduction in hippocampal CA1-CA3 volume (62% of control)

abnormal somatosensory cortex morphology ( J:182294 )

• decrease in cortical layer thickness at the somatosensory cortex; decrease in thickness of cortical layers II/III, V, and VI, but no difference in layer IV

• 25% decrease in thickness of cortical layers V and VI

• density of NeuN-labeled neurons in layers V and VI of the somatosensory cortex is increased by 27%, however density in layer II/III and IV is normal

• while there is a decrease in thickness of layers V and VI of the somatosensory cortex, the density of neurons in these layers is increased, indicating that the total number of neurons is unchanged

Genotype
MGI:3613564

ht3

• Allelic Composition: Dyrk1a^tm1Mla/Dyrk1a⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:78597 )

• about 30% of heterozygotes die during the first 3 days of life

• 70% of heterozygotes survive by the end of the preweaning period

growth/size/body

microcephaly ( J:102616 )

decreased body size ( J:78597 )

• heterozygotes surviving to adulthood are significantly smaller than wild-type mice

decreased body weight ( J:78597 )

• surviving heterozygotes display a significant reduction in body weight during the entire preweaning period

• after weaning, both male and female heterozygotes maintain a lower body weight, with an average reduction of 30%

decreased body length ( J:78597 )

• surviving heterozygotes display a significant reduction in body length during the entire preweaning period

nervous system

decreased hindbrain size ( J:78597 )

• adult heterozygotes exhibit a severe size reduction of the hindbrain

decreased brain size ( J:78597 )

• the brains of adult heterozygotes are ~30% smaller than those of wild-type mice, with mid- and hindbrain regions being severely reduced relative to forebrain structures, and ventral brain regions (e.g. hypothalamus, pons, and medulla oblongata) being more severely affected than dorsal structures (e.g. cerebellum or neocortex)

• in spite of size differences, no obvious malformations are observed in the lamination of the olfactory bulb, neocortex, hippocampus, and cerebellar cortex or in the structure of the striatum, thalamus, hypothalamus, and brain stem

decreased brain weight ( J:78597 )

• adult heterozygotes exhibit a disproportionate weight reduction in the cerebellum (including the posterior mesencephalon)

decreased midbrain size ( J:78597 )

• adult heterozygotes exhibit a severe size reduction of the midbrain

decreased superior colliculus size ( J:78597 )

• adult heterozygotes show a specific decrease in the number of neurons in the superior colliculus, which displays a notable size reduction

small tectum ( J:78597 )

• adult heterozygotes display a significantly reduced mesencephalic tectum

abnormal cerebral cortex pyramidal cell morphology ( J:102616 )

• adult heterozygous males exhibit a 45% reduction in the size of basal dendritic arbors of layer III pyramidal cells, associated with a 38% reduction in total dendritic length, a 48% decrease in dendritic spine density, altered distribution of spines, and a 35% reduction in the size of pyramidal cell somata

abnormal premotor cortex morphology ( J:102616 )

• at 7 months, heterozygous males display a 30% increase in neuron density in the second motor area (M2) of layer III pyramidal cells associated with altered neocortical pyramidal cell structure, suggesting a reduction in the complexity of circuits in the mature cerebral cortex

liver/biliary system

decreased liver weight ( J:78597 )

• adult heterozygotes exhibit a disproportionate decrease in liver weight

cardiovascular system

decreased heart weight ( J:78597 )

• adult heterozygotes have a lighter heart; however, the decrease in heart weight is proportional to the general decrease in body weight