Adult intestinal epithelium consists of a sheet of single-cell thickness which is morphologically highly organized into tubular invaginations (crypts) and finger-like projections (villi). Proliferation of the cells is confined to the base of the crypts, from which cells migrate to the villi, where they are shed. The villi are formed during embryogenesis from a multilayered epithelium. In mice, crypts develop at about the time of birth from the epithelium between the villi, which by this stage is no longer multilayered. So far it has remained unknown how many progenitor cells contribute to each crypt, and whether they develop by the proliferation of already committed progenitors, or as a result of local inductive tissue interactions. Here, we have used mouse aggregation chimaeras as an experimental system to demonstrate immunohistochemically that the epithelium of individual crypts in small and large intestine of adult mice is always composed of cells of a single parental type. We have confirmed that this result is not an artefact of the chimaeric system by examining female mice that are mosaic for the X-linked alleles Pgk-1a and Pgk-1b. We conclude that the epithelium of each adult crypt is derived from a single progenitor cell.

Animals↗

PubMedDate not supplied

HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.

Embryonal stem (ES) cell lines, established in culture from peri-implantation mouse blastocysts, can colonize both the somatic and germ-cell lineages of chimaeric mice following injection into host blastocysts. Recently, ES cells with multiple integrations of retroviral sequences have been used to introduce these sequences into the germ-line of chimaeric mice, demonstrating an alternative to the microinjection of fertilized eggs for the production of transgenic mice. However, the properties of ES cells raise a unique possibility: that of using the techniques of somatic cell genetics to select cells with genetic modifications such as recessive mutations, and of introducing these mutations into the mouse germ line. Here we report the realization of this possibility by the selection in vitro of variant ES cells deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT; EC 2.4.2.8), their use to produce germline chimaeras resulting in female offspring heterozygous for HPRT-deficiency, and the generation of HPRT-deficient preimplantation embryos from these females. In human males, HPRT deficiency causes Lesch-Nyhan syndrome, which is characterized by mental retardation and self-mutilation.

Adenine Phosphoribosyltransferase↗

PubMedDate not supplied

Genomic imprinting. Memories of mother and father.

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Animals↗