# SCID MICE AND THE CONTROL OF LYMPHOCYTE DIFFERENTIATION

> **NIH NIH R01** · INSTITUTE FOR CANCER RESEARCH · 1988 · $241,905

## Abstract

Normal lymphocyte maturation is blocked in mutant C.B-17scid mice;
consequently, they lack functional T and B cells.  However, some scid mice
are "leaky" (approximately 15%); i.e., they spontaneously produced large
quantities of immunoglobulin (Ig); preliminary evidence suggests that the B
cells responsible are few in number and may all derive from a common B
lymphocyte stem cell (B-LSC).  We propose to test this possibility in
several ways using Igh allotypes and novel Igh gene rearrangements as
clonal markers.  Assuming that monoclonality will apply to most leaky scid
mice, we will evaluate the capacity of B-LSC for lymphocyte generation and
replacement (persistence and quantity of Igh allotype levels) and diversity
(number and kind of Igh-V genes expressed).  This capacity will be compared
to that of less committed hematopoietic stem cells (HSC).  That is, we will
deliberately make scid mice "leaky" by reconstitution with B (and T)
lymphocyte progency of a single normal HSC.  Reconstitution will be
accomplished by co-transfer of limiting numbers of BALB/c (Igh-a) and
C.AL-20 (Igh-d) fetal liver cells into C.B-17scid (Igh-b) neonates (and
embryos).  Igh allotypes will serve as clonal markers.  Varying the
genotype and age of donors and recipients will enable us to examine both T
and B cell lineages and the effect of different microenvironments on stem
cell growth and differentiation.

The value of the scid mouse model for the proposed study is that it enables
us to assay the in vivo potential of stem cells at different stages of
development and in the context of a normal developmental progression.  Many
reconstituted scid mice may show unrestricted lymphoid differentiation;
i.e.; both T and B lymphocyte replacement.  Leaky scid mice, on the other
hand, should enable us to study restricted lymphoid differentiation; i.e.,
B lymphocyte generation in the absence of T cells and in the absence of
recruitment of less committed HSC (functional T cells have not yet been
detected in any scid mice).

## Key facts

- **NIH application ID:** 3125427
- **Project number:** 5R01AI013323-13
- **Recipient organization:** INSTITUTE FOR CANCER RESEARCH
- **Principal Investigator:** MELVIN J BOSMA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $241,905
- **Award type:** 5
- **Project period:** 1976-05-01 → 1991-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125427

## Citation

> US National Institutes of Health, RePORTER application 3125427, SCID MICE AND THE CONTROL OF LYMPHOCYTE DIFFERENTIATION (5R01AI013323-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125427. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*