Phenotypes Associated with This Genotype

Genotype
MGI:3810648

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

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

mortality/aging

premature death ( J:139866 )

• no mice survive beyond 3 months of age

postnatal lethality, incomplete penetrance ( J:139866 )

• the majority of pups fail to survive to weaning

• median survival is 18 days

nervous system

nervous system phenotype ( J:139866 )

N • brain weight is not significantly decreased and the major anatomical areas of the forebrain are not significantly different from controls

abnormal pituitary gland morphology ( J:138868 )

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

• however, the posterior lobe is similar in size to that in controls

abnormal pituitary gland development ( J:138868 )

• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland

• no change in proliferation in the posterior lobe

small pituitary gland ( J:138868 )

abnormal brain development ( J:139866 )

• increases in the numbers of Olig2+ glial and BLBP+ neuroglial progenitors are seen throughout the brain

• expression analysis indicates abnormalities in development and differentiation of neocortical neurons

abnormal hippocampus morphology ( J:139866 )

• at 1 week of age, an increase in proliferating cells is seen in the CA2/3 region

• however, when normalized to the number of progenitor cellsno increase in the percentage of proliferating cells is detected

abnormal secondary somatosensory cortex morphology ( J:139866 )

• decrease in the distance between the corpus callosum and the brain surface in the secondary somatosensory cortex indicating a reduction in cortex thickness

• pre- and post-natal treatment with Rolipram restores normal somatosensory cortical thickness

abnormal CNS glial cell morphology ( J:139866 )

• increase in the number of NG2+ glial cells in the brain including the somatosensory cortex

abnormal astrocyte morphology ( J:139866 )

• increase in the number of GFAP+ astrocytes in the brain

• gene-dose dependent increase in the number of astrocytes in the CA1 region of the hippocampus

increased oligodendrocyte number ( J:139866 )

• increase in the number of APC+ oligodendroglial cells in the brain including the fimbria

abnormal dendrite morphology ( J:139866 )

• apical dendrites of layer II/III pyramidal neurons in the somatosensory cortex are shorter compared to littermate controls

• pre- and post-natal treatment with Rolipram partially restores neurite length

abnormal nervous system physiology ( J:139866 )

• decrease in intracellular cAMP levels in the brain

abnormal neuronal precursor proliferation ( J:139866 )

• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells

abnormal pituitary gland physiology ( J:138868 )

• significant reduction in growth hormone and prolactin mRNA levels

abnormal hypothalamus physiology ( J:138868 )

• 50% reduction in cAMP levels in hypothalamic homogenates

growth/size/body

decreased body weight ( J:138868 , J:139866 )

• greater than 60% reduction in body weight compared to controls by 3 weeks of age (J:138868)

• weigh about 30% of the weight of control littermates at 2 - 3 months of age (J:138868)

• Rolipram treatment increases body weight but mice are still smaller than controls (J:138868)

• at P18, weight is less than 50% that of control littermates (J:139866)

postnatal growth retardation ( J:138868 , J:139866 )

• severe growth retardation develops during the first week after birth (J:138868)

• develop progressive growth retardation from P3 (J:139866)

• all major organ systems, except the central nervous system, display growth retardation at P18 (J:139866)

endocrine/exocrine glands

abnormal pituitary gland morphology ( J:138868 )

small adenohypophysis ( J:138868 )

• significantly smaller than control littermates

• however, the posterior lobe is similar in size to that in controls

abnormal pituitary gland development ( J:138868 )

• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland

• no change in proliferation in the posterior lobe

small pituitary gland ( J:138868 )

abnormal pituitary gland physiology ( J:138868 )

• significant reduction in growth hormone and prolactin mRNA levels

homeostasis/metabolism

abnormal hormone level ( J:138868 )

• decrease in growth hormone releasing hormone levels in the primary capillaries of the hypophyseal portal system

decreased circulating growth hormone level ( J:138868 )

• a 65% reduction in liver Igf1 mRNA levels indicates a reduction in circulating growth hormone levels

behavior/neurological

abnormal behavior ( J:139866 )

• extreme sensitivity to handling

abnormal voluntary movement ( J:139866 )

• limited range of movement of the hindlimbs

cellular

abnormal neuronal precursor proliferation ( J:139866 )

• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:138868