Phenotypes associated with this allele

• Allele Symbol: Tbr1^tm1Jlr
• Allele Name: targeted mutation 1, John L Rubenstein
• Allele ID: MGI:2179766
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbr1^tm1Jlr/Tbr1^tm1Jlr	involves: 129X1/SvJ	MGI:3040613
ht2	Tbr1^tm1Jlr/Tbr1^+	B6.129X1-Tbr1^tm1Jlr	MGI:5752313
cn3	Fezf2^tm1.1Nses/Fezf2^tm1.1Nses Tbr1^tm1Jlr/Tbr1^tm1Jlr Tg(Emx1-cre)#Ito/0 Tg(Mbp-MAPT/EGFP)#Eja/0	involves: 129S1/Sv * C57BL/6	MGI:5433181
cx4	Tbr1^tm1Jlr/Tbr1^tm1Jlr Tg(Mbp-MAPT/EGFP)#Eja/0	involves: 129X1/SvJ	MGI:5433182

Genotype
MGI:3040613

hm1

• Allelic Composition: Tbr1^tm1Jlr/Tbr1^tm1Jlr
• Genetic Background: involves: 129X1/SvJ

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

mortality/aging

postnatal lethality, complete penetrance ( J:51888 )

• animals die by the second postnatal day

behavior/neurological

aphagia ( J:51888 )

• homozygous pups do not feed

nervous system

decreased brain size ( J:51888 )

abnormal forebrain morphology ( J:51888 )

• disruption of the laminar structure of the cortical neurons, reduced number of preplate neurons and their derivatives

abnormal olfactory bulb development ( J:51888 )

• failure to form normal projection neurons (mitral and tufted cells) in the olfactory bulb

abnormal olfactory bulb interneuron morphology ( J:51888 )

• disorganization of the interneuron cell bodies due to absence of an intact mitral cell layer

• the granule cell layer and glomerular/external plexiform layer appear as a single layer

• striking reduction in mature olfactory bulb projection neurons

abnormal olfactory bulb external plexiform layer morphology ( J:51888 )

• the granule cell layer and glomerular/external plexiform layer appear as a single layer

abnormal olfactory bulb tufted cell morphology ( J:51888 )

• failure to form normal tufted cells

abnormal olfactory bulb glomerular layer morphology ( J:51888 )

• the glomerular layer contains 3-4 smaller glomeruli in its radial dimension rather than the 1-2 glomeruli seen in wild-type mice

abnormal olfactory bulb mitral cell layer morphology ( J:51888 )

• absence of an intact mitral cell layer

abnormal mitral cell morphology ( J:51888 )

• failure to form normal mitral cells

olfactory bulb hypoplasia ( J:51888 )

• due to reduced number of cells

abnormal olfactory cortex morphology ( J:51888 )

• hypoplastic olfactory cortex

abnormal olfactory tract morphology ( J:51888 )

• absence of axonal projections from the olfactory bulb to the primary olfactory cortex consistent with absence of projection neurons

Genotype
MGI:5752313

ht2

• Allelic Composition: Tbr1^tm1Jlr/Tbr1⁺
• Genetic Background: B6.129X1-Tbr1^tm1Jlr

behavior/neurological

abnormal conditioned taste aversion behavior ( J:208050 )

• in the conditioned taste aversion after training with LiCl injection, mutants do not recognize sucrose as a hazardous food and drink more sucrose than water

• treatment with D-Cycloserine ameliorates the conditioned taste aversion defect

abnormal cued conditioning behavior ( J:208050 )

• mice exhibit defective auditory fear conditioning, showing a lower freezing response when examined for auditory fear memory

• treatment with D-Cycloserine ameliorates the auditory fear conditioning defect

• however, mice do not exhibit deficits in open-field and elevated plus-maze tests or in novel object recognition or contextual fear conditioning

impaired social transmission of food preference ( J:208050 )

• mice do not show a preference for the cued food in an assay for social transmission of food preference

cognitive inflexibility ( J:208050 )

• in the appetitive-motivated T maze, during reversal learning, mice take a longer amount of time to realize that the reward had been changed to the other am in the T-maze indicating impaired cognitive flexibility

• in the two-choice digging test, mice take more trials to relearn that food had been moved to the bowl filled with cinnamon-flavored sawdust

abnormal social investigation ( J:208050 )

• mice show deficits in sociability in the three-chamber test, but not in preference for social novelty

• in a test of reciprocal social interaction, mice spend less time interacting with unfamiliar mice

• treatment with D-Cycloserine, a partial agonist of NMDA receptors, ameliorates the social interaction defects

decreased vocalization ( J:208050 )

• pups isolated from their mothers produce fewer ultrasonic vocalization emissions

nervous system

abnormal anterior commissure morphology ( J:208050 )

• posterior part of the anterior commissure is missing

abnormal amygdala morphology ( J:208050 )

• mice rarely show long processes extending from amygdalar neurons

• amygdalar neurons grown in culture develop multiple axons and each axon is shorter at 4 days in vitro compared to wild-type neurons

• however, cortical and striatal neuron morphology is normal

abnormal innervation ( J:208050 )

• the inter-amygdalar connections are greatly diminished

• defects in the connection between the ipsilateral central amygdala and basolateral amygdala

abnormal neuron physiology ( J:208050 )

• neuronal activation in the amygdala is impaired

• treatment with D-Cycloserine increases neuronal activity in the amygdala

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:208050

Genotype
MGI:5433181

cn3

• Allelic Composition: Fezf2^tm1.1Nses/Fezf2^tm1.1Nses; Tbr1^tm1Jlr/Tbr1^tm1Jlr; Tg(Emx1-cre)#Ito/0; Tg(Mbp-MAPT/EGFP)#Eja/0
• Genetic Background: involves: 129S1/Sv * C57BL/6

Aberrant L6 projections to the brainstem in the Tbr1^tm1Jlr/Tbr1^tm1Jlr mice require Fezf2

nervous system

nervous system phenotype ( J:169221 )

N • unlike Tbr1^tm1Jlr homozygotes, mice lack retrograde labeling of L5 and L6 projection neurons

Genotype
MGI:5433182

cx4

• Allelic Composition: Tbr1^tm1Jlr/Tbr1^tm1Jlr; Tg(Mbp-MAPT/EGFP)#Eja/0
• Genetic Background: involves: 129X1/SvJ

Premature overgrowth and superabundance of subcortical axons in the brainstem of Tbr1^tm1Jlr/Tbr1^tm1Jlr Tg(Mbp-MAPT/EGFP)#Eja/0 mice

nervous system

abnormal innervation ( J:169221 )

• mice exhibit ectopic projections to the brainstem identified by retrograde tracing