The kreisler mouse: a hindbrain segmentation mutant that lacks two rhombomeres.
kreisler is a recessive mutation resulting in gross malformation of the inner ear of homozygous mice. The defects in the inner ear are related to abnormalities in the hindbrain of the embryo, adjacent to the ear rudiments. At E9.5, the neural tube posterior to the boundary between the third and fourth rhombomeres, r3 and r4, appears unsegmented, and the region that would normally correspond to r4 is unusually thick-walled and contains many dying cells. The absence of morphological segmentation in the posterior hindbrain corresponds to an altered pattern of gene expression in that region, with major abnormalities posterior to the r4/5 boundary and minor abnormalities anterior to it. From the expression patterns at E9.5 of Krox-20, Hoxb-1 (Hox 2.9), Hoxb-2 (Hox 2.8), Hoxa-3 (Hox 1.5), Hoxd-4 (Hox 4.2) and cellular retinoic-acid binding protein I (CRABP I), it appears that the fundamental defect is a loss of r5 and r6. Correspondingly, the glossopharyngeal ganglion and nerve, associated with r6 are missing and the abducens nerve, which originates from r5 and r6, is also absent. Examination of Krox-20 expression at stages as early as E8.5 indicates that Krox-20 fails ever to be expressed in its r5 domain in the homozygous kreisler mutant. The abnormal amount of cell death is seen only later. An interpretation is that the cells that would normally become specified at an early stage as r5 and r6 adopt an r4 character instead, producing an excess of r4 cells that is disposed of subsequently by cell death.
McKay
I J
IJ
Department of Zoology, Oxford University, UK.
Muchamore
I
I
Krumlauf
R
R
Maden
M
M
Lumsden
A
A
Lewis
J
J
D000818:Animals; D016923:Cell Death / Q000502:physiology; D003391:Cranial Nerves / Q000002:abnormalities; D007758:Ear, Inner / Q000002:abnormalities*; D015870:Gene Expression / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000002:abnormalities* / Q000196:embryology / Q000235:genetics; D012249:Rhombencephalon / Q000002:abnormalities*