Phenotypes associated with this allele

• Allele Symbol: Fgf2^tm1Zllr
• Allele Name: targeted mutation 1, Rolf Zeller
• Allele ID: MGI:2384003
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgf2^tm1Zllr/Fgf2^tm1Zllr	involves: 129S1/Sv * 129X1/SvJ	MGI:3716192
hm2	Fgf2^tm1Zllr/Fgf2^tm1Zllr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3693850
cx3	Fgf2^tm1Zllr/Fgf2^tm1Zllr Fgf6^tm1Thbr/Fgf6^tm1Thbr	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:3716191
cx4	Dmd^mdx/? Fgf2^tm1Zllr/Fgf2^tm1Zllr Fgf6^tm1Thbr/Fgf6^tm1Thbr	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/10ScSn	MGI:3716189
cx5	Dmd^mdx/? Fgf2^tm1Zllr/Fgf2^tm1Zllr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn	MGI:3716196

Genotype
MGI:3716192

hm1

• Allelic Composition: Fgf2^tm1Zllr/Fgf2^tm1Zllr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

muscle

muscle phenotype ( J:85088 )

N • mice do not show any changes in the musculature compared to double and triple mutants carrying the Dmd^mdx allele; no dystrophic muscle fibers are detected

Genotype
MGI:3693850

hm2

• Allelic Composition: Fgf2^tm1Zllr/Fgf2^tm1Zllr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal neuronal migration ( J:49141 )

• in newborn homozygotes, a fraction of neuronal progenitors fail to colonize their target cortical layers III and II during cerebral cortex development; as a result, a greater number (~17%) of BrdU-labeled cells remain in the deeper cortical layers (VI-IV) and the corpus callosum relative to wild-type mice (~8.8%)

• this defect is variable, as many more BrdU-positive cells (25-36%) are found in the corpus callosum and deep layers of severely affected homozygotes, whereas a few others are indistinguishable from wild-type

• adult homozygotes display varying degrees of ectopic parvalbumin-positive neurons in the hippocampal commissure

abnormal hippocampal commissure morphology ( J:49141 )

• adult homozygotes display varying degrees of ectopic parvalbumin-positive neurons in the hippocampal commissure located beneath the cerebral cortex

abnormal cerebral cortex morphology ( J:49141 )

• at birth, homozygotes show defects in organization and differentiation of the cerebral cortex

decreased cerebral cortex pyramidal cell number ( J:49141 )

• at birth, only a few differentiated, large pyramidal neurons are detected in the cerebral cortex

abnormal stratification in cerebral cortex ( J:49141 )

• at birth, all differentiating cortical layers appear compressed and less distinct

loss of cortex neurons ( J:49141 )

• an average reduction of ~25% in parvalbumin-positive neurons is observed in all cortical layers

• however, no differences in the distribution of astroglial cells are observed

• no significant differences are noted in cell survival in either embryonic (E16), newborn or adult cerebral cortex, as shown by TUNEL analysis

thin cerebral cortex ( J:49141 )

• at birth, the thickness of the cerebral cortex is reduced by ~10%

abnormal spinal cord grey matter morphology ( J:49141 )

• adult homozygotes show neuronal abnormalities throughout the mantle layer of the cervical spinal cord, with only a few differentiated large neurons while all other neural cell types appear normal

abnormal baroreceptor physiology ( J:49141 )

• adult homozygotes respond normally to chronic angiotensin II infusion but show an impaired baroreceptor reflex

• in response to an acute vasodilatory stimulus (isoproterenol), all homozygotes, but no wild-type mice, display a significant drop in blood pressure along with an impaired increase in heart rates, indicating autonomic dysfunction

cardiovascular system

hypotension ( J:49141 )

• on average, the blood pressure of adult homozygotes is reduced by ~10 mmHg relative to wild-type littermates

• however, no differences in baseline plasma renin values, heart rates or body weights are observed

behavior/neurological

behavior/neurological phenotype ( J:49141 )

N • homozygotes do NOT develop seizures or reeler-like phenotypes

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:104949 )

N • homozygotes exhibit normal inner ear morphogenesis with no detectable abnormalities at the adult stage

N • in addition, homozygotes show no significant differences in hearing thresholds before and after noise-induced cochlear damage relative to wild-type littermates

cellular

abnormal neuronal migration ( J:49141 )

• in newborn homozygotes, a fraction of neuronal progenitors fail to colonize their target cortical layers III and II during cerebral cortex development; as a result, a greater number (~17%) of BrdU-labeled cells remain in the deeper cortical layers (VI-IV) and the corpus callosum relative to wild-type mice (~8.8%)

• this defect is variable, as many more BrdU-positive cells (25-36%) are found in the corpus callosum and deep layers of severely affected homozygotes, whereas a few others are indistinguishable from wild-type

• adult homozygotes display varying degrees of ectopic parvalbumin-positive neurons in the hippocampal commissure

Genotype
MGI:3716191

cx3

• Allelic Composition: Fgf2^tm1Zllr/Fgf2^tm1Zllr; Fgf6^tm1Thbr/Fgf6^tm1Thbr
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

muscle

muscle phenotype ( J:85088 )

N • mice do not show any changes in the musculature compared to double and triple mutants carrying the Dmd^mdx allele; no dystrophic muscle fibers are detected

abnormal myoblast migration ( J:85088 )

• basal level of migration of mutant myoblasts in culture is reduced by ~one-third relative to wild-type; migratory response to stimulation by Fgf2 and Fgf6 is significantly increased but does not reach level of stimulated wild-type myoblasts

cellular

abnormal myoblast migration ( J:85088 )

• basal level of migration of mutant myoblasts in culture is reduced by ~one-third relative to wild-type; migratory response to stimulation by Fgf2 and Fgf6 is significantly increased but does not reach level of stimulated wild-type myoblasts

Genotype
MGI:3716189

cx4

• Allelic Composition: Dmd^mdx/?; Fgf2^tm1Zllr/Fgf2^tm1Zllr; Fgf6^tm1Thbr/Fgf6^tm1Thbr
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/10ScSn

muscle

muscle phenotype ( J:85088 )

N • growth and differentiation kinetics of myogenic cells are comparable to wild-type

abnormal skeletal muscle morphology ( J:85088 )

• pale areas in muscle contain extensive connective tissue

abnormal skeletal muscle fiber morphology ( J:85088 )

• when mice are injected with the diazo dye EBD, dye is taken up by damaged muscle fibers to varying degrees, but preferentially into the hindlimb; uptake occurs because of focal breakdown of plasmalemma which is an early event in necrosis

• some muscles are stained entirely indicating massive damage to the muscle fibers of the diaphragm and gluteus maximus whereas muscles in wild-type mice do not take up dye

increased variability of skeletal muscle fiber size ( J:85088 )

• in pale areas of muscles, remaining myotubes show large variation in caliber size

skeletal muscle fiber necrosis ( J:85088 )

• numerous necrotic fibers are present

decreased satellite cell number ( J:85088 )

• myotubes have slightly reduced percentage of satellite cells with respect to myotube nuclei in wild-type (3.05% vs 3.56%)

dystrophic muscle ( J:85088 )

• severe abnormalities are observed

abnormal muscle physiology ( J:85088 )

• mutants display palpable stiffness of the musculature, most evident in pelvic and shoulder girdle, at up to 6 months of age

skeleton

abnormal spine curvature ( J:85088 )

• up to 6 months of age, mice do not show clinical signs of severe dystrophy except for dorsal-ventral curvature of the spine

Genotype
MGI:3716196

cx5

• Allelic Composition: Dmd^mdx/?; Fgf2^tm1Zllr/Fgf2^tm1Zllr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10ScSn

muscle

dystrophic muscle ( J:85088 )

• mutants show dystrophic changes to the muscle fibers, although less severely than Fgf2/Fgf6/Dmd triple mutants

• changes are not enhanced compared to Dmd mutants