Mouse Genome Informatics
cn
    Nf1tm1Par/Nf1tm1Par
Tg(Fabp7-cre)2Gtm/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• the majority of pups fail to survive to weaning
• median survival is 18 days
• no mice survive beyond 3 months of age

nervous system
N
• brain weight is not significantly decreased and the major anatomical areas of the forebrain are not significantly different from controls (J:139866)
• significantly smaller than control littermates
• however, the posterior lobe is similar in size to that in controls
• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland
• no change in proliferation in the posterior lobe
• 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
• 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
• 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
• increase in the number of NG2+ glial cells in the brain including the somatosensory cortex
• 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
• increase in the number of APC+ oligodendroglial cells in the brain including the fimbria
• 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
• decrease in intracellular cAMP levels in the brain
• increase in proliferation at E13.5 and to a lesser extent at E17.5 primarily in neuroglial progenitor cells
• significant reduction in growth hormone and prolactin mRNA levels
• 50% reduction in cAMP levels in hypothalamic homogenates

growth/size/body
• 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)
• 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
• significantly smaller than control littermates
• however, the posterior lobe is similar in size to that in controls
• 3-fold reduction in proliferating cells in the anterior lobe of the pituitary gland
• no change in proliferation in the posterior lobe
• significant reduction in growth hormone and prolactin mRNA levels

homeostasis/metabolism
• decrease in growth hormone releasing hormone levels in the primary capillaries of the hypophyseal portal system
• a 65% reduction in liver Igf1 mRNA levels indicates a reduction in circulating growth hormone levels

behavior/neurological
• extreme sensitivity to handling
• limited range of movement of the hindlimbs

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

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:138868