# REVERSE GENETICS OF A LEUKEMIA SUSCEPTIBILITY LOCUS

> **NIH NIH R01** · NEW YORK UNIVERSITY · 1991 · $275,262

## Abstract

Our laboratory wishes to define, localize and study the mode of action of
genes involved in susceptibility/resistance to x-irradiation-induced
leukemia.  We have recently identified the major locus involved in
susceptibility to fractionated irradiation (FX)-induced leukemia, Ril-1.
We have now detected polymorphism among congenic mouse strains differing at
Ril-1 with a cloned DNA probe specific for the spleen focus forming virus
(SFFV).  When DNA from these congenic mice is digested with restriction
enzyme PvuII, a 5.7 kb fragment is present is susceptible (C57BL/6) but not
resistant (B6.C-H-30c) mice.  Since these mice are identical at most genes,
except Ril-1, and tightly linked genes, the PvuII fragment in question must
be encoded by Ril-1 or tightly linked loci.  Further studies have shown
that the probable distance of the fragment from Ril-1 is 0-60 kilobases.
Therefore, it now appears possible to clone Ril-1.  Starting with the 5.7
kb PvuII fragments we propose to first derive a single copy probe specific
for cellular sequences in the Ril-1 region, then isolate the complete gene
from lambda and/or cosmid libraries.  Such gene(s) will be micro-injected
into embryos, and transfected into transplanted bone marrow cells in order
to unequivocally demonstrate their functional role in FX-induced leukemia.
In addition, experiments will be performed to try to understand the
mechanism of Ril-1 action in FX-induced leukemia.  These experiments will
include measurement of (1) temporal changes in mRNA levels or size of
transcripts, (2) rearrangements or translocation of Ril-1 DNA sequences,
(3) the activation of Ril-1 on subsets of lymphocytes, and (4) the
development of serological reagents for Ril-1 to aid in biochemical and
cellular studies of the gene product(s).

## Key facts

- **NIH application ID:** 3173057
- **Project number:** 5R01CA035482-07
- **Recipient organization:** NEW YORK UNIVERSITY
- **SAM.gov UEI:** NX9PXMKW5KW8
- **Principal Investigator:** DANIEL MERUELO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $275,262
- **Award type:** 5
- **Project period:** 1984-03-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173057

## Citation

> US National Institutes of Health, RePORTER application 3173057, REVERSE GENETICS OF A LEUKEMIA SUSCEPTIBILITY LOCUS (5R01CA035482-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173057. Licensed CC0.

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