normal cerebellar function, phenotypic crosses of 
the lurcher {Id) and meander tail (mea) neurologi- 
cal mutants with Mus castaneous have been used 
to map these genetic defects on mouse chromo- 
somes 6 and 4, respectively. The well-studied semi- 
dominant mutation Ic results in degeneration and 
death of essentially all cerebellar Purkinje cells, 
commencing at about postnatal day 10. The fully 
recessive mutation mea results in skeletal abnor- 
malities in the tail, as well as cerebellar abnormali- 
ties. Since no detailed analysis of the mea pheno- 
type has yet been published. Dr. Heintz's 
laboratory (in collaboration with Drs. Carol Mason 
and Mary Beth Hatten, Columbia University College 
of Physicians and Surgeons) has initiated an in- 
depth study of cerebellar anatomy in the mea 
mouse. The adult mea homozygote displays normal 
foliation and cytoarchitecture in the posterior lobes 
of the cerebellum. However, the anterior lobes of 
the mea cerebellum are characterized by the gross 
disorganization of the Purkinje cells, the absence of 
granule cells, and disorientation of radial glia. The 
facts that the transition from normal to grossly ab- 
PUBLICATIONS 
normal cytoarchitecture occurs very rapidly in the 
mea cerebellum, that the transition occurs in the 
same position in different animals, and that this 
line of demarcation is present as early as postnatal 
day 8 suggest that the mea gene product defines a 
specific developmental compartment in the mam- 
malian brain. Present efforts are aimed at saturating 
the genetic map surrounding these neurological 
phenotypes with anonymous DNA probes and con- 
structing long-range physical maps in the appropri- 
ate genetic interval, in preparation for cloning the 
Ic and mea genes. 
A second cloning effort, which involves the use of 
subtractive cloning and plus/minus screening of li- 
braries prepared from RNA isolated from either 
wild-type or mutant animals is under way. The ob- 
ject of this work is to isolate a wide variety of genes 
that are expressed either in specific cell types or 
with a specific developmental profile in the mouse 
cerebellum. 
Dr. Heintz is also Associate Professor and Univer- 
sity Fellow at The Rockefeller University. 
Articles 
Dailey, L., Roberts, S.B., and Heintz, N. 1988. Purification of the human histone H4 gene-specific transcrip- 
tion factors H4TF-1 and H4TF-2. Genes Dev 2:1700-1712. 
Gallinari, R, La Bella, F., and Heintz, N. 1989. Characterization and purification of H1TF2, a novel CCAAT- 
binding protein that interacts with a histone HI subtype-specific consensus element. Mol Cell Biol 
9:1566-1575. 
Heintz, N. 1989. Temporal regulation of gene expression during the mammalian cell cycle. Curr Opinion Cell 
Biol 1:275-278. 
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