Phenotype Image Detail

Image

Caption

Foliation defects and postnatal neurodegeneration in the cerebellum of Cers1^tm1.1Kwi/Cers1^tm1.1Kwi (CerS1-/-) mice. A-C, cerebellum and brain stem (dorsal aspect) as seen in an adult wild-type (CerS1+/+) mouse (A) and mutant mice of 2 months (B) and 12 months (C) of age. Note the progressive shrinkage of the cerebellum first evident by the retraction of the anterior vermis (asterisk) from the caudal colliculi already at 2 months. Shrinkage of cerebellar hemispheres (Hem) starts more slowly and is most pronounced during the second half of the 1st year postnatally. Dotted lines indicate the border between the vermis and hemispheres. Note that the flocculonodular lobe almost retains its normal size. At 12 months, the cerebellum is reduced to a flat band covering the dorsal pons. However, the relative loss of volume still appears greatest in the vermal region. Quantitatively, the postnatal cerebellum from 6-week-old mice loses about 50% of its normal weight (D). Interestingly, a limited weight loss is seen in heterozygous mice. Bars represent mean + S.E. (error bars) of weight of cerebellum. Stars indicate statistically significant difference, when compared with wild-type controls (***, p<0.001; t test). E and F, Mutant mice feature a modified cerebellar foliation pattern already during postnatal development characterized by the absence of a short fissure separating lobules VI and VII (arrow) and less consistently by the absence of a short fissure splitting the apical part of lobule IX (arrowhead). G-J, neurodegeneration affects both Purkinje neurons (G and H) and granule cells (I and J). Loss of Purkinje cells, visualized here by anti-calbindin staining in G and H and marked by arrows in I, mainly starts after completion of lamina formation around postnatal day 20 and leads to a subtotal loss of these cells by the end of the first year. Due to their extremely high number, loss of granule cells is on first glance less impressive in routine preparations of early adult cerebella, mainly identified by small cysts filled with debris (circle in I) and an unusually wide scattering of cells in an internal granular layer now more dominated by interstitial territories of mossy fiber boutons (arrowheads in I). However, a strongly increased extent of granule cell apoptosis is already present in postmigratory cells of the anterior lobe (J), the first cerebellar region showing shrinkage. Bars represent mean + S.E. (error bars) of apoptotic cells per area. K and L, in contrast to the mainly neuronal damage, astrogliosis is most prominent in the cerebellar white matter but surprisingly less so in neuronal strata. However, this finding again shows that changes in the axonal sphingolipid profile might have an impact on different cell types. Mes, mesencephalon. Calibration bars, 2 mm in A, B and C, 1 mm in E and F, 150 um in G and H, 50 um in I, and 750 um in K and L.

Copyright

This image is from Ginkel C, J Biol Chem 2012 Dec 7;287(50):41888-902 and is displayed with the permission of the American Society for Biochemistry and Molecular Biology who owns the Copyright. Full text from JBC. J:193419

Associated Alleles

Symbol	Name
Cers1^tm1.1Kwi	ceramide synthase 1; targeted mutation 1.1, Klaus Willecke

Associated Genotypes

Allelic Composition	Genetic Background
Cers1^tm1.1Kwi/Cers1^tm1.1Kwi	involves: 129P2/OlaHsd * C57BL/6