Phenotypes associated with this allele

• Allele Symbol: Foxb1^tm1Pgr
• Allele Name: targeted mutation 1, Peter Gruss
• Allele ID: MGI:2384086
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxb1^tm1Pgr/Foxb1^tm1Pgr	B6.129-Foxb1^tm1Pgr	MGI:3813479
hm2	Foxb1^tm1Pgr/Foxb1^tm1Pgr	involves: 129S1/Sv * 129X1/SvJ	MGI:2384397
hm3	Foxb1^tm1Pgr/Foxb1^tm1Pgr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2384398
ht4	Foxb1^tm1Pgr/Foxb1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813478

Genotype
MGI:3813479

hm1

• Allelic Composition: Foxb1^tm1Pgr/Foxb1^tm1Pgr
• Genetic Background: B6.129-Foxb1^tm1Pgr

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

nervous system

abnormal hypothalamus morphology ( J:100811 )

• at P56, homozygotes show an abnormal mammillary region in the caudal hypothalamus

abnormal mammillary body morphology ( J:100811 )

• notably, supramammillary nuclei and the hippocampal region remain intact

• at P56, adult homozygotes lack medial mammillary nuclei (MMn) and a large portion of the lateral mammillary neurons

• in adults, the area in the posterior hypothalamus previously occupied by MMn is reduced and filled with cell-sparse neuropils

• the mammillary axonal tree is severely reduced, comprising a thin principal mammillary tract and a barely detectable mammillotegmental tract, along with a small group of rostrally directed axons ending around the ventral thalamus

• a relatively large and still visible fornix bundle is present, probably due to the survival of a part of the lateral mammillary nuclei

behavior/neurological

behavior/neurological phenotype ( J:100811 )

N • adult homozygotes exhibit no deficits in hippocampal-dependent tasks such as contextual and cued fear conditioning tests and social transmission of food preference

N • in addition, homozygotes are not impaired in the spatial reference memory test in the eight-arm radial arm maze

abnormal spatial learning ( J:100811 )

• homozygotes display deficits in a specific subset of spatial tasks which require combined use of both spatial and working memory functions

• adult homozygotes are impaired in acquisition of the spatial memory version of the Barnes circular maze (where the escape hole is not marked), with only 18% of homozygotes exhibiting a spatial strategy versus 78% and 82% of wild-type and heterozygous mice, respectively, at the end of training

• however, homozygotes are as proficient as wild-type and heterozygous animals in the acquisition and performance of the cued version of the Barnes maze, in which an escape hole is direclty marked

abnormal spatial working memory ( J:100811 )

• adult homozygotes show deficits in spatial working memory tasks, including the spontaneous alternation and the working memory test in the radial arm maze

Genotype
MGI:2384397

hm2

• Allelic Composition: Foxb1^tm1Pgr/Foxb1^tm1Pgr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

neonatal lethality, incomplete penetrance ( J:44764 )

• homozygotes are viable at birth; however, ~30% die within the first 2 days after birth

postnatal lethality, incomplete penetrance ( J:44764 )

• ~20% of homozygotes die prior to weaning, however, surviving homozygotes show a normal lifespan

growth/size/body

decreased body size ( J:44764 )

• surviving homozygotes remain proportionally smaller (25-30%) than wild-type littermates

decreased body weight ( J:44764 )

• surviving homozygotes show a 25-30% weight reduction relative to wild-type mice throughout their entire lifespan

postnatal growth retardation ( J:44764 )

• homozygotes that survive the early neonatal period become growth retarded within the first week of age

• the growth rate of homozygotes remains slower until weaning; afterwards, the rate of growth is similar to that of wild-type littermates

behavior/neurological

abnormal sexual interaction ( J:44764 )

• homozygotes show poor mating performance on a 129/Sv genetic background

Genotype
MGI:2384398

hm3

• Allelic Composition: Foxb1^tm1Pgr/Foxb1^tm1Pgr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:44764 )

• at 4 weeks of age, only 10.3% (versus expected 25%) of homozygotes are obtained from heterozygous crosses

• the majority of homozygotes die before weaning

growth/size/body

decreased body weight ( J:44764 )

• homozygotes show a pronounced weight reduction within the first three weeks after birth

• surviving homozygotes never reach the weight of wild-type littermates in adulthood

postnatal growth retardation ( J:44764 )

behavior/neurological

abnormal maternal nurturing ( J:44764 )

♀ • mutant mothers neglect and spread their pups and fail to show nest-building or nursing activities; as a result, all pups die shortly after birth

♀ • nurturing behavior is not improved after multiple pregnancies

abnormal nursing ( J:44764 )

♀ • female homozygotes are fertile but do not nurse their pups

♀ • lack of nursing is not secondary to a lactation defect, as mammary glands appear histologically and functionally normal

nervous system

abnormal midbrain morphology ( J:44764 )

• at 3 weeks of age, homozygotes show overt malformations in posterior midbrain

• however, no obvious midbrain structural anomalies are detected from E10.5 to E18.5

decreased inferior colliculus size ( J:44764 )

• at 3 weeks of age and thereafter, mutant inferior colliculi in the caudal brain are reduced near the midline and partially or totally covered by the anterior cerebellum (lobulus culmen)

• in contrast, superior colliculi remain largely unaffected

abnormal hypothalamus morphology ( J:44764 )

• at 3 weeks of age, the caudal hypothalamus is severely abnormal

abnormal mammillary body morphology ( J:44764 )

• as early as E16.5, the size of the medial region of the mammillary body is reduced

• at E18.5, the medial mammillary nucleus fails to develop and the mammillothalamic tract appears disorganized

• at 3 weeks of age, the prominent medial mammillary nucleus is absent, disrupting the layered structure of the entire mammillary body and causing a size reduction of the efferent mammillothalamic and the mammillotegmental tracts

• as a result, the adjacent supramammillary nucleus is misshapen and extends more ventrally

• other nuclei of the ventro-caudal hypothalamus appear less compact, and the distance between the third ventricle and the mammillary recess is reduced

abnormal cerebellum morphology ( J:44764 )

• at 3 weeks of age, homozygotes display an overgrowth (elongation) of the most anterior cerebellar lobe (lobulus culmen)

• at this age, the distance between anterior cerebellum and the superior colliculi is significantly reduced due to the reduction of inferior colliculi and the overgrowth of anterior cerebellum

abnormal cerebellum anterior vermis morphology ( J:44764 )

• at 3 weeks of age, homozygotes show an elongation of the most anterior lobe of the cerebellar vermis

cellular

maternal effect ( J:44764 )

• all pups born to homozygous mutant mothers die shortly after birth due to abnormal nurturing behavior

• however, all homozygotes obtained from heterozygous crosses are born live at the expected Mendelian frequency

Genotype
MGI:3813478

ht4

• Allelic Composition: Foxb1^tm1Pgr/Foxb1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal midbrain morphology ( J:44764 )

• at 3 weeks of age, heterozygotes display an intermediate phenotype in the posterior midbrain region relative to wild-type and homozygous mutant mice

• however, the heterozygous caudal hypothalamus remains unaffected and no alterations in the mammillary body are observed

decreased inferior colliculus size ( J:44764 )

• at 3 weeks of age, heterozygotes show an intermediate size reduction in the medial portion of inferior colliculi relative to wild-type and homozygous mutant mice

• however, the size of the most anterior cerebellar lobe, the lobulus culmen, remains unaffected