Phenotypes associated with this allele

• Allele Symbol: Tle5^tm1Grid
• Allele Name: targeted mutation 1, Tom Gridley
• Allele ID: MGI:2180116
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tle5^tm1Grid/Tle5^tm1Grid	involves: 129S1/Sv * C57BL/6J	MGI:3039487
cx2	Tle5^tm1Grid/Tle5^tm1Grid Runx2^tm1Mjo/Runx2^+	involves: 129S1/Sv * C57BL/6	MGI:3582296
cx3	Tle5^tm1Grid/Tle5^tm1Grid Notch1^tm1Grid/Notch1^+	involves: 129S1/Sv * C57BL/6J	MGI:3039488

Genotype
MGI:3039487

hm1

• Allelic Composition: Tle5^tm1Grid/Tle5^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

premature death ( J:29516 )

• homozygous mutant mice were born alive and survived the early postnatal period

• however, approximately 20% of mutant mice died within the first 5 weeks after birth

growth/size/body

postnatal growth retardation ( J:29516 )

• the first group (approximately 20%) of mutant mice appeared severely affected in their postnatal growth: this runting phenotype was detectable a few days after birth, and at weaning age the average weight of this class of homozygous mutant mice was ~40% that of their wild-type and heterozygous littermates; these mice became progressively less active and died within the first 5 weeks after birth

• the second group (approximately 80%) of mutant mice displayed a much milder runting phenotype

• the postnatal growth rate of all homozygous mutant mice was slower than that of their wild-type littermates

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:86317 )

N • at P1, total pituitary growth hormone content is comparable to wild-type

abnormal pituitary gland morphology ( J:86317 )

• contains a substantial patch of cells of indeterminate fate

• cells in midsection of the pituitary dorsal to lumen are primarily POMC +ve; this region is relatively small, comprising ~6% of total gland volume

abnormal pituitary diverticulum morphology ( J:86317 )

• mutants exhibit a varying degree of dorsal dysmorphology, with dorsal bifurcation detectable at E14.5 through birth

• abnormalities in the shape of the lumen of Rathke's pouch are noted

bifurcated Rathke's pouch ( J:86317 )

• dorsal bifurcation detectable at E14.5 through birth

enlarged pituitary gland ( J:86317 )

• volume of gland is larger than in wild-type mice

behavior/neurological

abnormal mating frequency ( J:29516 )

• when homozygous mutant males and females were mated to each other or to wild-type C57BL/6J animals, normal size litters were obtained

• however, while homozygous mutant males normally mated with wild-type females within the first three days, it typically took several days or even weeks to obtain copulation plugs in homozygous mutant females when mated to either wild-type C57BL/6J males or to homozygous mutant males

nervous system

abnormal pituitary gland morphology ( J:86317 )

• contains a substantial patch of cells of indeterminate fate

• cells in midsection of the pituitary dorsal to lumen are primarily POMC +ve; this region is relatively small, comprising ~6% of total gland volume

abnormal pituitary diverticulum morphology ( J:86317 )

• mutants exhibit a varying degree of dorsal dysmorphology, with dorsal bifurcation detectable at E14.5 through birth

• abnormalities in the shape of the lumen of Rathke's pouch are noted

bifurcated Rathke's pouch ( J:86317 )

• dorsal bifurcation detectable at E14.5 through birth

enlarged pituitary gland ( J:86317 )

• volume of gland is larger than in wild-type mice

Genotype
MGI:3582296

cx2

• Allelic Composition: Tle5^tm1Grid/Tle5^tm1Grid; Runx2^tm1Mjo/Runx2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

skeleton

clavicle hypoplasia ( J:92187 )

• these mutants possess hypoplastic clavicles with no medial cartilaginous anlage, similar to the phenotype observed in Runx2 heterozygotes

decreased bone mineral density ( J:92187 )

• at 1 week after birth, these mutants display a phenotype of osteopenia, which worsens at 2-4 weeks after birth

abnormal skeleton development ( J:92187 )

• these mutants show reduced skeletal development and growth relative to control littermates

abnormal fontanelle morphology ( J:92187 )

• these mutants exhibit a more severe defect in fontanelle closure relative to heterozygous Runx2 mice

abnormal long bone hypertrophic chondrocyte zone ( J:92187 )

• these mutants show expansion of the resting zone and thinner zones of proliferation and hypertrophy in the growth plate relative to control littermates

decreased width of hypertrophic chondrocyte zone ( J:92187 )

• the growth plates of the tibia and humerus show reduced thickness due to a reduction in the thickness of the proliferative as well as the hypertrophic zones

decreased long bone epiphyseal plate size ( J:92187 )

• these mutants show an exacerbated reduction in the overall height of growth plates of the tibia and humerus, and in the amount of trabecular bone subjacent to the growth plates relative to Aes homozygous null littermates

• this severe growth plate defect is largely attributed to reduced Ihh signaling

growth/size/body

decreased body weight ( J:92187 )

• 80% of these mutants display body weights in the range of 28-75% of control wild-type or Aes heterozygous null littermates

• the weights of ~20% of these mice are less than 50% the weight of wild-type littermates; the weights of ~30% are between 50% and 60% of wild-type weights

• no sex differences are noted during the first 5 weeks of postnatal growth; however, subsequently the weight differences between female mutant and wild-type mice are not as large as they are in males

disproportionate dwarf ( J:92187 )

• at 1 week after birth, these mutants display a phenotype of dwarfism, which progressively worsens at 2-4 weeks after birth

• although mutants recover to some extent after 5 weeks of age, they remain consistently smaller than their littermates

postnatal growth retardation ( J:92187 )

• these mutants exhibit significant individual variation in the severity of the growth defect

• males are severely affected and remain small up to 6 months of age; in contrast, the weight and size of female mutants approach wild-type values after 2-3 months of age

craniofacial

abnormal fontanelle morphology ( J:92187 )

• these mutants exhibit a more severe defect in fontanelle closure relative to heterozygous Runx2 mice

reproductive system

female infertility ( J:92187 )

♀ • the cause of female infertility requires further investigation

male infertility ( J:92187 )

♂ • the cause of male infertility requires further investigation

Genotype
MGI:3039488

cx3

• Allelic Composition: Tle5^tm1Grid/Tle5^tm1Grid; Notch1^tm1Grid/Notch1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J

growth/size/body

postnatal growth retardation ( J:29516 )

• these compound mutant mice were born in normal numbers, but showed the same degree of runting as mutant mice homozygous for an Aes null allele