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The crypt cycle in mouse small intestinal epithelium

Y Q Li¹, S A Roberts, U Paulus

¹CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.

Journal of Cell Science

|December 1, 1994

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Investigating the mouse intestinal crypt cycle using a mutation marker system, this study found a surprisingly long crypt cycle of approximately 3.6 years in control mice. This suggests most crypts divide only once during a mouse's lifespan.

Area of Science:

Gastroenterology
Molecular Biology
Genetics

Background:

The intestinal epithelium is maintained by stem cells within crypts.
Understanding the crypt cycle and fission is crucial for tissue regeneration and cancer research.
The Dlb-1 locus influences Dolichos biflorus agglutinin (DBA) binding, serving as a marker for intestinal crypts.

Purpose of the Study:

To investigate the frequency of intestinal crypt fission and the crypt cycle duration.
To utilize a mutation-induced marker system for tracking crypt dynamics.
To assess the impact of mutagens on crypt mutation and regeneration.

Main Methods:

Utilized mice heterozygous at the Dlb-1 locus (Dlb-1b/Dlb-1a).
Employed whole-mount preparations stained with Dolichos biflorus agglutinin peroxidase conjugate (DBA-Px).

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Quantified the frequency of DBA-Px negative crypt clusters over time in control and mutagen-treated mice.

Main Results:

Spontaneous mutations at the Dlb-1b locus created DBA-Px negative crypts.
The crypt cycle in control mice was estimated to be very long: 187 +/- 44 weeks (approximately 3.6 years).
Mutagen treatment (N-nitroso-N-ethylurea, N-methyl-N'-nitro-N-nitrosoguanidine) increased mutation frequency.

Conclusions:

The mouse intestinal crypt cycle is significantly longer than previously thought.
A substantial proportion of crypts may undergo only a single division during a mouse's lifetime.
The mutation marker system provides a viable method for studying crypt dynamics and the effects of genotoxic agents.