Phenotypes associated with this allele

• Allele Symbol: Bhlhe22^tm1Gan
• Allele Name: targeted mutation 1, Lin Gan
• Allele ID: MGI:3707409
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bhlhe22^tm1Gan/Bhlhe22^tm1Gan	involves: 129S7/SvEvBrd	MGI:3830526
hm2	Bhlhe22^tm1Gan/Bhlhe22^tm1Gan	involves: 129S7/SvEvBrd * C57BL/6	MGI:3707542
cn3	Bhlhe22^tm1Gan/Bhlhe22^tm2(cre)Gan Tg(CAG-Bgeo/GFP)21Lbe/0	involves: 129S/Sv * 129X1/SvJ * C57BL/6J	MGI:3830525

Genotype
MGI:3830526

hm1

• Allelic Composition: Bhlhe22^tm1Gan/Bhlhe22^tm1Gan
• Genetic Background: involves: 129S7/SvEvBrd

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

nervous system

decreased brain size ( J:144066 )

• at 1 week, brain volume is slightly decreased compared to in wild-type mice

• however, this was not due to changes in apoptosis rates

abnormal pyramidal decussation morphology ( J:144066 )

abnormal cerebral cortex morphology ( J:144066 )

• layer V of the sensorimotor cortex exhibits a subtle laminar abnormality with compaction of its sublayers unlike in wild-type mice

• area-specific gene expression in the somatosensory and caudal motor cortices is disrupted compared to in wild-type mice indicating a disruption in molecular identity

• however, the rostral motor domain does not expand at the expense of the caudal sensory domain, and rostral identity is not suppressed

• subcerebral projection neuron (SCPN) and caudal corticospinal motor neuron (CSMN) molecular features are lost in the caudal motor cortex

abnormal somatosensory cortex morphology ( J:144066 )

• area-specific gene expression in the somatosensory and caudal motor cortices is disrupted compared to in wild-type mice indicating a disruption in molecular identity

disorganized barrel cortex ( J:144066 )

abnormal nervous system tract morphology ( J:144066 )

• axons from the caudal motor cortex in 2 of 3 mice pass through the internal capsule and cerebral peduncle but stop at the base of the pons with no fibers entering the medullary pyramidal tract, pyramidal dessucation or ventral dorsal funiculus unlike in wild-type mice

abnormal anterior corticospinal tract morphology ( J:144066 )

• in adult mice, the medullary pyramidal tract is dramatically reduced in size compared to in wild-type mice

abnormal corticospinal tract morphology ( J:144066 )

• while a small number of fibers of the reduced pyramidal tract enter the pyramidal decussation in the medulla there is an absence of the spinal portion of the corticospinal tract unlike in wild-type mice

• corticospinal motor neuron axons from the rostral motor cortex pass through the internal capsule, cerebral peduncle and brainstem pyramidal tract but stop at the medullary pyramidal dessucation unlike in wild-type mice

abnormal motor neuron morphology ( J:144066 )

• subcerebral projection neuron (SCPN) and caudal corticospinal motor neuron (CSMN) molecular features are lost in the caudal motor cortex

growth/size/body

decreased body weight ( J:144066 )

• body weight is reduced 14% and 40% at P7 and 1 month of age, respectively, compared to wild-type mice

Genotype
MGI:3707542

hm2

• Allelic Composition: Bhlhe22^tm1Gan/Bhlhe22^tm1Gan
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

vision/eye

decreased amacrine cell number ( J:119663 )

• the total number of amacrine cells in the inner nuclear layer and ganglion layer is reduced

• GABAergic amacrine cell numbers are reduced by 44.2+/-6%, a significant reduction of TH+ amacrine cells is seen and Prox1+ displaced amacrine cells are absent

• the generation of GABAergic and type 2 cone bipolar amacrine subtypes is reduced

• Prox1+ displaced amacrine cells are not generated

abnormal retina cone bipolar cell morphology ( J:119663 )

• Vsx1+ cone bipolar cells are reduced by 36.3+/-7%

• however, other subtypes are unaffected

• the generation of type 2 OFF cone bipolar cells is reduced

thin retina inner nuclear layer ( J:119663 )

• the inner nuclear layer (INL) is reduced in thickness

growth/size/body

decreased body weight ( J:119663 )

• display signs of slower weight gain compared to control littermates at ~about 3 weeks of age

nervous system

decreased amacrine cell number ( J:119663 )

• the total number of amacrine cells in the inner nuclear layer and ganglion layer is reduced

• GABAergic amacrine cell numbers are reduced by 44.2+/-6%, a significant reduction of TH+ amacrine cells is seen and Prox1+ displaced amacrine cells are absent

• the generation of GABAergic and type 2 cone bipolar amacrine subtypes is reduced

• Prox1+ displaced amacrine cells are not generated

abnormal retina cone bipolar cell morphology ( J:119663 )

• Vsx1+ cone bipolar cells are reduced by 36.3+/-7%

• however, other subtypes are unaffected

• the generation of type 2 OFF cone bipolar cells is reduced

integument

skin lesions ( J:119663 )

• develop skin lesions between 1 and 2 months of age

Genotype
MGI:3830525

cn3

• Allelic Composition: Bhlhe22^tm1Gan/Bhlhe22^tm2(cre)Gan; Tg(CAG-Bgeo/GFP)21Lbe/0
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal corticospinal tract morphology ( J:144066 )

• at P0, no Bhlhe22-expression fibers are detected in the medullary pyramidal tract unlike in wild-type mice

• in adults, few Bhlhe22-expression fibers are detected in the medullary pyramidal tract unlike in wild-type mice

• Bhlhe22-expression fibers present in the decussation do not enter the ventral dorsal funiculus of the spinal cord unlike in wild-type mice

• fewer than normal subcerebral projection neurons enter the medullary pyramidal tract while caudal corticospinal motor neurons fail to enter the tract